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INTRODUCTION Over the last few decades, the development landscape of small molecule drugs has been significantly impacted by various biotechnology breakthroughs. Further, with the advent of novel technologies, biologics have made a significant impact in the pharmaceutical domain, delivering ground-breaking treatment for a myriad of disease indications, including immunological, oncological and rare disorders.

New York, Sept. 29, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Biopharmaceutical Contract Manufacturing Market by Type of Service Offered, Type of Biologic Manufactured, Type of Expression System Used, Scale of Operation, Company Size, and Key Geographical Regions : Industry Trends and Global Forecasts, 2022 2035" - https://www.reportlinker.com/p06323412/?utm_source=GNW In this context, it is worth highlighting those 14 biopharmaceutical products (including cell therapies, gene therapies, monoclonal antibodies and recombinant proteins) were approved in the US alone, in 2021. Further, promising results from ongoing clinical research initiatives have encouraged various government and private firms to make significant investments in this domain. For instance, in 2021, a sum of over USD 70 billion was invested in the cell and gene therapy domain. However, manufacturing of biologics is fraught with various challenges. Some of the key concerns of contemporary innovators include rate of attrition of pipeline drugs / therapies, prolonged development timelines, current facility limitations, regulatory and compliance-related issues, and inconsistencies related to quality attributes of the final product. Therefore, therapy developers are actively exploring avenues that enable them to overcome the existing challenges. Amongst other alternatives, outsourcing has emerged as a lucrative option for biologic drug developers.

Currently, a significant number of players engaged in the biopharmaceutical domain prefer to outsource various operations to contract service providers. In fact, currently over 275 companies claim to offer contract manufacturing services for biologic therapeutics, in compliance with the regulatory standards. It is also worth highlighting that biopharmaceutical contract manufacturers are actively trying to consolidate their presence in this field by entering into strategic alliances in order to meet the indubitably rising demand for biologics. For this purpose, substantial expansions, and mergers and acquisitions have been reported in this market, as service providers strive to become one-stop-shops, to cater to the diverse needs of their clientele. With outsourcing being increasingly accepted as a viable and beneficial business model within this field, we anticipate the biopharmaceutical contract manufacturing market to grow at a commendable pace in the coming years.

SCOPE OF THE REPORTThe Biopharmaceutical Contract Manufacturing Market by Type of Service(s) Offered (API, FDF), Type of Biologic Manufactured (Antibodies, Cell Therapies, Vaccines and Other Biologics), Type of Expression System Used (Mammalian, Microbial and Others), Scale of Operation (Preclinical / Clinical and Commercial), Company Size (Small, Mid-sized, and Large and Very Large), and Key Geographical Regions (North America, Europe, Asia-Pacific, Latin America and MENA): Industry Trends and Global Forecasts, 2022 2035 report features an extensive study of the current market landscape and the likely future potential associated with the biopharmaceutical contract manufacturing market, over the next decade.

The study also includes a detailed analysis of key drivers and trends within this evolving market.

Amongst other elements, the report features:

A detailed overview of the overall landscape of companies engaged in offering contract manufacturing services for biologics, including a detailed analysis based on several relevant parameters, such as year of establishment, company size (based on number of employees), location of headquarters, type of service(s) offered (API and FDF manufacturing), type of biologic manufactured (ADCs, antibodies, biosimilars, cell therapies, gene therapies, nucleic acids / oligonucleotides, plasmid DNA / viral vectors, proteins / peptides, vaccines and others), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others), type of bioreactor used (single use, stainless steel and others) and mode of operation of bioreactor (batch, fed batch and perfusion / continuous).A detailed landscape of the biopharmaceutical manufacturing facilities established across the key geographical regions (North America, Europe, Asia-Pacific and Rest of the World), highlighting the manufacturing hubs for biologics.Elaborate profiles of key industry players based in North America, Europe and Asia-Pacific that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.A detailed discussion on the key enablers in this domain, including certain niche product classes, such as antibody drug conjugates (ADCs), bispecific antibodies, cell therapies, gene therapies and viral vectors, which are likely to have a significant impact on the growth of the contract services market.A case study on the growing global biosimilars market, highlighting the associated opportunities for biopharmaceutical CMOs and CDMOs.A case study comparing the key characteristics of small and large molecule drugs, along with details on the various steps involved in their respective manufacturing processes.A detailed discussion on the benefits and challenges associated with in-house manufacturing, featuring a brief overview of the various parameters that a drug / therapy developer may need to take into consideration while deciding whether to manufacture its products in-house or outsource the production operations.A qualitative analysis, highlighting various factors that need to be taken into consideration by biopharmaceutical developers while deciding whether to manufacture their respective products in-house or engage the services of a CMO.A review of the various biopharmaceutical-focused manufacturing initiatives undertaken by top 10 big pharma players (shortlisted on the basis of 2021 revenues), highlighting trends across various parameters, such as number of initiatives, year of initiative, purpose of initiative, type of initiative, scale of operation and type of biologic manufactured.An analysis of the recent collaborations within the biopharmaceutical contract manufacturing industry, based on several relevant parameters, such as year of partnership, type of partnership, type of biologic manufactured, therapeutic area, most active players (in terms of number of deals inked) and regional distribution of partnership activity that have taken place in this domain, during the period 2015-2022.A detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2022, based on several relevant parameters, such as year of agreement, type of deal, geographical location of companies, type of acquisition, type of biologic manufactured and key value drivers.A detailed review of expansion initiatives undertaken by biopharmaceutical contract manufacturers, during the period 2016-2022, along with information on several relevant parameters, such as year of expansion, purpose of expansion, type of biologic manufactured and location of expanded facility.An analysis of the recent developments within the biopharmaceutical contract manufacturing industry, highlighting information on the funding investments made during the period 2016-2022, along with information on the technology advancements related to biomanufacturing.An estimate of the overall, installed capacity for the manufacturing of biopharmaceuticals, based on information reported by various industry stakeholders in the public domain, highlighting the distribution of the available capacity, based on size of manufacturer (small, mid-sized and large and very large), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others) and geography (North America, Europe, Asia-Pacific and Rest of the World).An informed estimate of the annual demand for biologics, taking into account the top 20 biologics, based on various relevant parameters, such as target patient population, dosing frequency and dose strength of the abovementioned products.A company size-wise, detailed analysis of the total cost of ownership for biopharmaceuticals contract manufacturing organizations, during the period 2022-2042.A case study on the virtual business model concept, along with its role in the overall biopharmaceutical industry. It also features a discussion on the advantages and risks / challenges associated with outsourcing operations from virtual service providers.A discussion on affiliated trends, key drivers and challenges, under an elaborate SWOT framework, which are likely to impact the industrys evolution, including a Harvey ball analysis, highlighting the relative effect of each SWOT parameter on the overall biopharmaceutical industry.A survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing contract manufacturing services to biopharmaceutical developers.

One of the key objectives of the report was to estimate the existing market size and estimate the future size of biopharmaceutical contract manufacturing market. We have provided informed estimates on the evolution of the market, over the period 2022-2035. Our year-wise projections of the current and future opportunity have further been segmented on the basis of [A] type of service(s) offered (API, FDF), [B] type of biologic manufactured (antibodies, cell therapies, vaccines and other biologics), [C] type of expression system used (mammalian, microbial and others), [D] scale of operation (preclinical / clinical and commercial), [E] company size (small, mid-sized, and large and very large), and [F] key geographical regions (North America, Europe, Asia-Pacific, Latin America and MENA).

In order to account for future uncertainties associated with some of the key parameters and to add robustness to our forecast model, we have provided three market forecast scenarios, portraying the conservative, base and optimistic tracks of the markets evolution.

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

KEY QUESTIONS ANSWEREDWho are the key players engaged in offering contract manufacturing services for biopharmaceuticals?What are the different partnerships and expansion initiatives undertaken by biopharmaceutical contract manufacturers in the recent past?Which regions represent the current key contract manufacturing hubs for biopharmaceuticals?What is the current, installed capacity for contract manufacturing of biopharmaceuticals?What is the current, global demand for biologics? How is the demand for such candidates likely to evolve in the foreseen future?What percentage of the biopharmaceuticals manufacturing operations are presently outsourced?What factors should be taken into consideration while deciding whether the manufacturing operations for biopharmaceuticals should be kept in-house or outsourced?How is the current and future opportunity likely to be distributed across key market segments?

CHAPTER OUTLINES

Chapter 2 is an executive summary of key insights captured during our research. It offers a high-level view on the current state of biopharmaceutical contract manufacturing market and its likely evolution in the short to mid-term and long-term.

Chapter 3 provides a general introduction to biopharmaceuticals and biopharmaceutical manufacturing processes. The chapter also includes an overview of the various expression systems used for the development of different types of biotherapeutic products. It features a brief overview of contract manufacturing, along with a detailed discussion on the need for outsourcing within the biopharmaceutical industry. Furthermore, it provides information on the challenges faced by players currently engaged in this domain.

Chapter 4 provides a detailed assessment of the current market landscape of companies engaged in offering contract manufacturing services for biologics, including a detailed analysis based on several relevant parameters, such as year of establishment, company size (based on number of employees), location of headquarters, type of service(s) offered (API and FDF manufacturing), type of biologic manufactured (ADCs, antibodies, biosimilars, cell therapies, gene therapies, nucleic acids / oligonucleotides, plasmid DNA / viral vectors, proteins / peptides, vaccines and others), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others), type of bioreactor used (single use, stainless steel and others) and mode of operation of bioreactor (batch, fed batch and perfusion / continuous).

Chapter 5 provides a detailed landscape of the biopharmaceutical manufacturing facilities established across the key geographical regions (North America, Europe, Asia-Pacific and Rest of the World), highlighting the manufacturing hubs for biologics.

Chapter 6 provides elaborate profiles of key industry players based in North America that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.

Chapter 7 provides elaborate profiles of key industry players based in Europe that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.

Chapter 8 provides elaborate profiles of key industry players based in Asia-Pacific that offer contract manufacturing services for biologics. Each profile features a brief overview of the company, details related to its biologic-related service portfolio, manufacturing facilities, recent developments, and an informed future outlook.Chapter 9 provides a detailed discussion on the key enablers in this domain, including certain niche product classes, such as antibody drug conjugates (ADCs), bispecific antibodies, cell therapies, gene therapies and viral vectors, which are likely to have a significant impact on the growth of the contract services market.

Chapter 10 presents a case study on the growing global biosimilars market, highlighting the associated opportunities for biopharmaceutical CMOs and CDMOs.

Chapter 11 presents a case study comparing the key characteristics of small and large molecule drugs, along with details on the various steps involved in their respective manufacturing processes.

Chapter 12 provides a detailed discussion on the benefits and challenges associated with in-house manufacturing, featuring a brief overview of the various parameters that a drug / therapy developer may need to take into consideration while deciding whether to manufacture its products in-house or outsource the production operations.Chapter 13 presents a qualitative analysis, highlighting various factors that need to be taken into consideration by biopharmaceutical developers while deciding whether to manufacture their respective products in-house or engage the services of a CMO.

Chapter 14 provides a review of the various biopharmaceutical-focused manufacturing initiatives undertaken by top 10 big pharma players (shortlisted on the basis of 2021 revenues), highlighting trends across various parameters, such as number of initiatives, year of initiative, purpose of initiative, type of initiative, scale of operation and type of biologic manufactured.

Chapter 15 presents an analysis of the recent collaborations within the biopharmaceutical contract manufacturing industry, based on several relevant parameters, such as year of partnership, type of partnership, type of biologic manufactured, therapeutic area, most active players (in terms of number of deals inked) and regional distribution of partnership activity that have taken place in this domain, during the period 2015-2022.

Chapter 16 provides a detailed analysis of the various mergers and acquisitions that have taken place within this domain, during the period 2015-2022, based on several relevant parameters, such as year of agreement, type of deal, geographical location of companies, type of acquisition, type of biologic manufactured and key value drivers.

Chapter 17 presents a detailed review of expansion initiatives undertaken by biopharmaceutical contract manufacturers, during the period 2016-2022, along with information on several relevant parameters, such as year of expansion, purpose of expansion, type of biologic manufactured and location of expanded facility.

Chapter 18 presents an analysis of the recent developments within the biopharmaceutical contract manufacturing industry, highlighting information on the funding investments made during the period 2016-2022, along with information on the technology advancements related to biomanufacturing.

Chapter 19 provides an estimate of the overall, installed capacity for the manufacturing of biopharmaceuticals, based on information reported by various industry stakeholders in the public domain, highlighting the distribution of the available capacity, based on size of manufacturer (small, mid-sized, and large and very large), scale of operation (preclinical, clinical and commercial), type of expression system used (mammalian, microbial and others) and geography (North America, Europe, Asia-Pacific and Rest of the World).

Chapter 20 presents an informed estimate of the annual demand for biologics, taking into account the top 20 biologics, based on various relevant parameters, such as target patient population, dosing frequency and dose strength of the abovementioned products.

Chapter 21 presents a company size-wise, detailed analysis of the total cost of ownership for biopharmaceuticals contract manufacturing organizations, during the period 2022-2042.

Chapter 22 presents an insightful market forecast analysis, highlighting the future potential of biopharmaceutical contract manufacturing market till 2035. We have segmented the market on the basis of type of service(s) offered (API, FDF), type of biologic manufactured (antibodies, cell therapies, vaccines and other biologics), type of expression system used (mammalian, microbial and others), scale of operation (preclinical / clinical and commercial) , company size (small, mid-sized, and large and very large), and key geographical regions (North America, Europe, Asia-Pacific, Latin America and MENA).

Chapter 23 presents a case study on the virtual business model concept, along with its role in the overall biopharmaceutical industry. It also features a discussion on the advantages and risks / challenges associated with outsourcing operations from virtual service providers.

Chapter 24 provides a discussion on affiliated trends, key drivers and challenges, under an elaborate SWOT framework, which are likely to impact the industrys evolution, including a Harvey ball analysis, highlighting the relative effect of each SWOT parameter on the overall biopharmaceutical industry.

Chapter 25 features an elaborate discussion on the future opportunities / trends within the biopharmaceutical contract manufacturing market that are likely to influence the growth of this domain over the coming years.

Chapter 26 provides a survey analysis featuring inputs solicited from various experts who are directly / indirectly involved in providing contract manufacturing services to biopharmaceutical developers.

Chapter 27 is a summary of the entire report. It provides the key takeaways and presents our independent opinion of the biopharmaceutical contract manufacturing market, based on the research and analysis described in the previous chapters.

Chapter 28 is a collection of transcripts of interviews conducted with various stakeholders in the industry.

Chapter 29 is an appendix, which provides tabulated data and numbers for all the figures provided in the report.

Chapter 30 is an appendix, which provides the list of companies and organizations mentioned in the report.Read the full report: https://www.reportlinker.com/p06323412/?utm_source=GNW

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Biopharmaceutical Contract Manufacturing Market by Type of Service Offered, Type of Biologic Manufactured, Type of Expression System Used, Scale of...

Recommendation and review posted by Bethany Smith

Introduction

Huntingtons disease (HD) is an autosomal dominant neurodegenerative disorder with an estimated prevalence of up to 9 per 100,000 in the USA, Canada, Oceania, and Western Europe.1,2 HD is caused by a CAG (cytosine, adenine, and guanine) repeat expansion in exon 1 of the Huntingtin (HTT) gene, resulting in the translation of a mutant Huntingtin protein harboring a toxic polyglutamine (polyQ) stretch at its amino (N) terminus. Gene carriers with repeats between 36 and 39 CAG show incomplete penetrance, while repeats of 40 and more triplets lead to fully penetrant disease. The age of onset is inversely correlated with the CAG repeat length, with an average age of onset of 3544 years. HD is characterized by motor, cognitive and psychiatric symptoms and is ultimately fatal, with a median survival of 1518 years after onset. About 510% of HD patients show disease onset before 20 years of age, in which case it is called juvenile HD. Juvenile HD has a different clinical presentation compared to adult onset HD, characterized by symptoms such as severe mental retardation, speech and language delay, as well as more pronounced motor and cerebellar symptoms and overall more rapid disease progression.3

Apart from the inherited CAG length, several genetic modifiers have been identified that are associated with age of onset. Many of these modifiers point towards an important role for somatic instability: the process in which the CAG repeat within cells expands over time. Within the HTT locus, a strong genetic modifier is whether or not a CAA (cytosine, adenine, and adenine) interruption is present at the 3 end of the CAG repeat. Similar to CAG triplets, CAA encodes for glutamine, thus resulting in the same polyQ stretch. Nonetheless, alleles that lack this CAA interruption were found to be more prone to somatic expansion and showed decreased age of onset, while the presence of an additional CAA interruption was found to delay both somatic expansion and age of onset.4,5 Moreover, many of the identified trans-acting genetic modifiers, such as FANCD2 And FANCI Associated Nuclease 1 (FAN1) and MutL Homolog 1 (MLH1), are involved in DNA mismatch repair and influence somatic instability of the CAG repeat.5,6

Although HD was initially thought to be mainly a protein toxic gain-of-function disorder, it is likely that protein loss-of-function also plays a role, as reviewed elsewhere,710 and there is increasing evidence for the involvement of other disease mechanisms, such as repeat-associated non-AUG dependent (RAN) translation and RNA toxic gain-of-function, also reviewed previously.1113 Still, little is known regarding the relative contribution of each of these pathogenic mechanisms to the disease (Figure 1).

Figure 1 Schematic overview of the molecular pathogenesis of HD.

HTT is known to be essential for embryonic development, as demonstrated by the fact that knockout mice are embryonically lethal, and also appears to play a role in later stages of development and life, as reviewed by Kaemmerer and Grondin.10 There is, however, no clear consensus on the level of wild type HTT (wtHTT) that is required for its normal function, as this is likely to depend on many factors, including age and tissue/brain region. wtHTT is involved in many important cellular processes, including endocytosis and vesicular trafficking, cell division, autophagy and transcriptional regulation (reviewed by Saudou and Humbert)9 which may all be impacted by a loss of wtHTT function in HD.

Compelling evidence for the involvement of RNA-mediated toxicity was provided by Sun et al, who found that even in the absence of translation, there was still repeat-length dependent toxicity of 5 HTT mRNA as well as full-length HTT.14 RNA toxic gain-of-function is caused by the interaction between RNA-binding proteins (RBPs), such as Muscleblind like splicing regulator 1 (MBNL1) and Pre-mRNA processing factor 8 (PRPF8), and the secondary structure formed by the expanded CAG repeat in the mRNA, affecting the splicing of a range of transcripts.15,16 This interaction appears to be dependent on the purity of the CAG repeat (ie, the absence of CAA interruptions), as Mbnl1 was found to be recruited to nuclear foci in the novel BAC-CAG mouse model, which has an uninterrupted repeat, but not in the BACHD model, which harbors an interrupted repeat.17

Finally, the presence of the expanded CAG repeat has also been shown to induce repeat-associated non-AUG dependent (RAN) translation, which leads to the production of homopolymers other than polyQ that may also negatively impact cell function. RAN translation products have been detected in the affected brain regions of patients, as well as in N171-82Q mice and a C. elegans model.18,19 However, the actual contribution of RAN translation products to HD is not clear, as, for example, no RAN toxicity was observed in HD140Q knock-in mice.20

The expanded polyQ-containing mutant HTT (mHTT) protein has been shown to interact aberrantly with a variety of proteins, including transcriptional regulators such as RNA polymerase II subunit A (POLR2A), Tumor protein p53, Mouse double minute 2 (MDM2), CREB-binding protein (CBP) and Heat shock protein 70 (HSP70), cell cycle regulators like Ras homolog enriched in brain (Rheb) and mammalian target of rapamycin (mTOR), and cytoskeleton proteins such as actin and neurofilament light (NF-L). These aberrant interactions result in a complex and widespread molecular pathology, affecting many essential processes in the cell, including DNA damage repair, transcriptional regulation, mitochondrial function and apoptosis.2125 Importantly, premature polyadenylation of the pre-mRNA as well as proteolytic cleavage of HTT protein lead to the production of a variety of HTT fragments, and there is ample evidence that such fragments, especially the short N-terminal species, are more toxic than the full-length mHTT protein.2635 In order to make tailored therapeutics towards the short toxic fragments, a good understanding of the mechanisms leading to their formation is needed. In this review, we therefore focus on how toxic N-terminal HTT protein species are produced and how they are linked to toxicity, as well as on therapeutic strategies that are capable of reducing these fragments.

N-terminal HTT protein fragments are mainly produced through two distinct processes: proteolytic cleavage and premature polyadenylation (see Figure 2 and Table 1).

Table 1 Overview of Proteolytic Cleavage Sites

Figure 2 Schematic overview of production of N-terminal HTT protein. (A) Regular splicing, overview of the resulting mRNA and full-length protein and the identified proteolytic cleavage sites. (B) Alternative splicing and premature polyadenylation and resulting transcript. (C) Resulting protein species and propensity for nuclear entry, aggregation and toxicity.

The group of Michael Hayden first showed that HTT could be cleaved proteolytically by apopain (caspase-3) in a repeat-length dependent manner.36 This was confirmed in a follow-up study, in which they mapped one of the caspase-3 cleavage sites to D513 and another site C-terminally of amino acid (aa) 548. Furthermore, two caspase-1 cleavage sites were identified in the first 548 aa. In contrast to their previous work with truncated HTT, the authors found no repeat-length dependence of cleavage efficiency of full-length HTT.37 In a third study, the authors were able to map the second caspase-3 cleavage site to D552, and further identified a caspase-6 cleavage site at D586.38 More recently, Martin et al recently identified yet another caspase cleavage site at D572, which was shown to be cleaved by caspase-1 and caspase-2.39

Both full-length and N-terminal caspase-cleavage products of HTT were found to be substrates for cleavage by calpains.4042 Four calpain cleavage sites have been mapped, at aa 437, 465/469 and 536/54041 and between aa 63111,42 calpain cleavage efficiency appears to be positively correlated with repeat length.41,42 Furthermore, it was shown that calpain levels, and in particular the active form, were increased in the caudate of HD patients compared to controls.41

Next to caspase and calpain generated fragments, various other cleaved HTT products have been described. Lunkes et al identified two N-terminal HTT fragments, cp-A and cp-B, which appeared to be generated in transfected NG108 cells through cleavage by aspartic endopeptidases. The C-terminus of HTT cp-A fragment was mapped between aa 104114. N-terminal fragments with the same immunogenic properties were identified in nuclear inclusions in post mortem frontal cortex of HD patients.43

Similarly, Schilling et al identified an N-terminal fragment ending between aa 90115 in post mortem tissues from HD patients and N171-82Q mice, as well as in transfected HEK293 cells.44 Further investigation in a HEK293 cell model revealed that short, HTT cp-B-like fragments were efficiently processed to HTT cp-A-like fragments, while longer HTT fragments proved to be inefficient substrates. The C-terminus of the HTT cp-A-like fragments was mapped between aa 105 and 115124. Although similar in size to the fragment described by Lunkes et al, inhibition of aspartyl proteases did not affect the formation of the cp-A-like fragment, and the authors were unable to identify any protease that generates these HTT cp-A-like fragments, suggesting that i) the fragments are not the same or ii) that the cp-A-like fragment described by Schilling et al is the same fragment but generated by a novel protease, which may be cell-type dependent.45 Ratovitski et al identified two N-terminal fragments (HTT cp-1 and cp-2) in PC12 and HEK293 cells expressing full-length HTT with 21Q or 126153Q or a truncated N1212 HTT fragment with 15Q or 138Q.46 These fragments were similar in size to the previously described HTT cp-A and cp-B fragments but were not affected by inhibition of aspartic endopeptidases. In addition, they were not affected by deletion of aa 105114. In combination with the epitope mapping, this narrowed the C-terminus of the HTT cp-1 fragment down to between aa 90 and 105, shorter than the cp-A and cp-A-like fragments described by Lunkes et al43 and Schilling et al44,45 Based on the absence of identified proteases and on the fragment length, we speculate that the generation of these fragments could involve aberrant splicing (see Aberrant Splicing and Premature Polyadenylation), although this would require further investigation.

Finally, Landles et al showed fourteen different N-terminal HTT protein isoforms (fragments 114) in brain tissue from HdhQ150 KI mice, the three shortest of which (fragments 1214) were specific to mHTT.33 Some of these fragments could be linked to specific proteolytic cleavage events: fragment 7 terminated at a novel calpain cleavage site between aa 510654, fragment 8 appeared to correspond to the D586 caspase-6 cleavage product, fragment 9 was likely produced by cleavage at calpain site 536 and fragment 10 by caspase cleavage at D513. Lastly, fragment 13 was determined to correspond to HTT-ex1.

In summary, many different proteases have been found to act on mHTT and wtHTT, generating N-terminal and C-terminal HTT fragments. The availability of antibodies that can recognize these fragments, as well as the possibility to specifically inhibit certain proteases, have allowed mapping of various fragments, albeit with variable resolution. Nonetheless, for multiple fragments, the mechanisms of production remain to be identified.

Besides proteolytic cleavage, there are other mechanisms that lead to the generation of toxic N-terminal mHTT fragments. Sathasivam et al showed that incomplete splicing of intron 1 leads to the production of a short premature polyadenylated HTT-ex1 transcript in various HD mouse models and that this HTT-ex1 can be translated into a 90 aa N-terminal HTT-ex1 protein (based on 23Q). HTT-ex1 transcript was also found to be expressed in HD patient fibroblasts and cortex.47 In a follow-up study, Neueder et al confirmed that the HTT-ex1 transcript can be detected in patient-derived fibroblasts, as well as HD patient cerebellum, sensory motor cortex and hippocampus, with the highest expression levels measured in juvenile HD patient tissues.48 The HTT-ex1 transcript has also been detected by RNA-sequencing in various HD mouse models, including BACHD, BAC-CAG and HdhQ111.17 Both in vitro and in patient-derived tissues, the production of the HTT-ex1 transcript appears to be positively correlated with CAG repeat length, showing much higher expression in cells and tissues derived from juvenile HD patients.48,49

The current hypothesis is that HTT-ex1 formation is influenced by a combination of sequestration of spliceosome components such as U1 snRNP at the CAG repeat, leading to less efficient splicing of exon 1 to exon 2, and a reduced transcription rate, which leads to longer exposure of the cryptic polyA site in intron 1. Although the Bates group initially found evidence for the involvement of Serine and Arginine Rich Splicing Factor 6 (SRSF6) in HTT-ex1 formation,47,49 they later found that the silencing of Srsf6 in HD mouse models did not affect HTT-ex1 formation.50 It has therefore been hypothesized that multiple RNA-binding proteins may be involved in the missplicing of HTT-ex1.12 Regardless of the exact mechanisms involved, aberrant mHTT splicing is CAG repeat length dependent, suggesting that HTT-ex1 formation and associated toxicity would increase as somatic instability progresses in HD48 and that interventions targeting repeat expansion and HTT-ex1 may have therapeutic advantage.

Consistently accumulating evidence indicates that small N-terminal fragments containing extended polyQ tracts significantly contribute mHTT cellular mislocalization, aggregation and toxicity. Initial studies by the Ross group showed that transfection of N2a or HEK293 cells with full-length HTT with either 23Q or 82Q, or of truncated HTT N171-18Q or N63-18Q resulted in a diffuse cytoplasmic localization of the protein. In contrast, transfection with N171-82Q or N63-82Q led to more punctate labeling in both cytoplasm and nucleus, with the short N63-82Q construct showing the most prominent nuclear localization.51 The Hayden group found similar results, showing that N-terminal fragments of 427, 548 or more aa formed mainly perinuclear aggregates, while fragments up to 224 aa showed both cytoplasmic and nuclear aggregates. Furthermore, they found that pathogenicity depended both on repeat length and on fragment size.26,27

Barbaro et al found that, in Drosophila, shorter N-terminal fragments were more toxic and more prone to aggregate, with HTT-ex1 being by far the most toxic species.28 In mice, the R6/2 model that expresses only HTT-ex1 is by far the most swiftly progressing HD mouse model,52,53 while conditional suppression of HTT-ex1 has been shown to be neuroprotective.54 Recent in vitro studies by the Lashuel group confirm these results and further extend the findings by showing that the polyQ and Nt17 domains of HTT-ex1 synergistically modulate the aggregation propensity of HTT-ex1, with a key role of the Nt17 domain in regulating HTT-ex1 aggregation dynamics and subcellular localization and toxicity.34

There is conflicting evidence with regard to the pathogenicity of nuclear and cytoplasmic mHTT. Some groups have reported evidence that nuclear localization is required for toxicity. For example, the Greenberg group showed that adding a nuclear export signal to a N171 HTT fragment blocked its toxicity in transfected striatal neurons.55 In contrast, the Hayden group reported that neither the addition of a nuclear localization signal to a N548 HTT fragment nor the addition of a nuclear export signal to a N151 fragment altered the toxicity of those fragments, suggesting that both the nucleus and the cytoplasm are sites of HD toxicity.56 Trushina et al found that nuclear entry of mHTT only occurred after commitment of a cell to cell death. Therefore, the authors argue that nuclear mHTT localization may not be the primary event leading to toxicity.57

Intranuclear and neuropil aggregates have been observed in most HD animal models,17,30,31,5863 and the presence of aggregates containing N-terminal HTT fragments has also been confirmed in patient brains by multiple groups.40,64,65 However, various groups have shown that it is not the insoluble aggregates or inclusion bodies, but rather the soluble oligomers that are the more toxic species.6669 In fact, some groups have found evidence that the formation of intranuclear inclusions may be protective,55,70,71 as reviewed by Arrasate and Finkbeiner.72 Mechanistically, this may be explained by the fact that soluble mHTT-ex1 oligomers have more aberrant protein interactions than insoluble aggregates and inclusions.73 Importantly, the length of N-terminal protein species and the associated sequence context, as well as post-translational modifications, also appear to play an important role in the aggregation process.35,74,75 For more in-depth reviews on the role of post-translational modifications, we redirect elsewhere.76,77

Various approaches have been investigated to therapeutically lower the expression or reduce the toxicity of the mutant HTT protein. The proteolytic cleavage pathway can be targeted to reduce the formation of N-terminal mHTT protein species. Furthermore, the N-terminal part of the protein can be targeted to reduce aggregation and/or increase clearance of mHTT. Finally, mHTT can be targeted at the transcript or gene level. Here, we will focus on approaches that are able to target not only full-length HTT but also HTT-ex1 and other N-terminal mHTT species, considering their potential therapeutic advantage (see Table 2).

Table 2 Overview of Studies Targeting HTT Protein

Caspase inhibition has been shown to reduce the proteolytic cleavage of mHTT and to improve the HD phenotype in BACHD78 and HdhQ111 mice.79 These results are backed up by earlier studies, where mutation of caspase-6 cleavage sites slowed down disease progression in YAC128 mice.80 However, it is not clear to what extent the protective effects are due specifically to the reduction of N-terminal mHTT species, rather than a general protective effect of caspase inhibition, as caspase inhibition was also protective in R6/2 and malonate models of HD, which do not express caspase-cleavable mHTT.8183

Using a different approach, Evers et al showed that removal of the caspase-6 cleavage site by antisense oligonucleotide (ASO)-mediated skipping of (part of) exon 12 led to reduced levels of the N568 fragment in vitro and in vivo in wild type and YAC128 mice.84,85 Except for the absence of astrogliosis, no data are available regarding phenotypic effects of this ASO treatment.

None of these approaches have yet successfully been translated into the clinic, and although all may potentially decrease the formation of toxic mHTT fragments and have the potential of allele-specificity, mechanisms of RNA-associated toxicity would not be addressed.

Aptamers are single-stranded oligonucleotides that, through their tertiary structure, can interact with target molecules such as proteins. The Roy lab identified aptamers that bind specifically to mHTT with 51 or 103Q but not wtHTT with 20Q.86,87 The selected aptamers were shown to inhibit aggregation of recombinant mHTT-ex1 in cell-free assays and in yeast, as well as reducing oxidative stress and mitochondrial dysfunction.86 To our knowledge, this approach has not yet been tested in vivo.

Various antibodies have been expressed intracellularly as intrabodies to target the N-terminus of HTT. In vivo, such intrabodies are delivered using viral vectors. An excellent review on the use of intrabodies in various neurodegenerative diseases was written by Messer and Butler.88

Two groups of intrabodies have been tested most extensively (see Figure 3): those that bind to the N-terminus of HTT (VL12.3, scFv-C4) and those that recognize the proline-rich regions (PRRs) in HTT-ex1 (MW7, Happ1, Happ3, INT41). In addition, there is some literature about polyQ-binding intrabodies (MW1, MW2) and a more C-terminal intrabody derived from EM48 (scFv-EM48).

Figure 3 Anti-HTT Exon 1 intrabodies. (A) Antigens used to select the published anti-HTT intrabodies. (B) Specific binding identified by crystallography for scFvC4 and VL12.3.

Notes: Reproduced from Messer A, Butler DC. Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders. Neurobiol Dis. 2020;134(October 2019):104619. doi: 10.1016/j.nbd.2019.104619 under Creative Commons BY-NC-ND 4.0.88

Southwell et al showed that intrabodies that bind to the PRR, ie, MW7, Happ1 and Happ3, increase the turnover of mHTT-ex1 overexpressed in vitro. VL12.3, an intrabody that binds to the N-terminal 17 aa of HTT, did not affect turnover, but did increase the nuclear localization of mHTT-ex1.90 In vivo, the PRR-binding Happ1 was shown to be beneficial in five different HD mouse models. In contrast, VL12.3, while effective in a lentiviral HD model, was ineffective in YAC128 mice and had a detrimental effect in R6/2 mice.91 The authors later showed that the increased turnover mediated by the PRR-binding intrabodies is dependent on a calpain-chaperone-mediated autophagy-dependent mechanism and that this process is blocked by VL12.3,92 explaining the detrimental effects of VL12.3.

Although scFv-C4 also binds to the N-terminus of HTT,93 its predominant cytoplasmic localization appears to protect from the detrimental effects observed for VL12.3.89 The scFv-C4 intrabody was shown to have beneficial effects in various HD models, including in vitro models, Drosophila and different mouse models.9498

Two additional intrabodies have been investigated: scFv-EM48 and INT41. Like Happ1, scFv-EM48, which binds just C-terminally to the second PRR, was shown to increase turnover of mHTT, and improved motor function of N171-82Q mice.99 INT41, an intrabody that recognizes the same epitope as Happ1, but which has enhanced cytoplasmic solubility, was shown to improve cognitive function in female R6/2 mice.100

In addition to the increased turnover induced by some of the intrabodies, the endogenous cellular machinery can be harnessed specifically to target proteins for degradation, using engineered proteins, peptides or small molecules. These can direct the protein of interest to the ubiquitin proteasome system, the autophagy-lysosomal pathway or chaperone-mediated autophagy. These approaches and their specific application in the context of HD have been extensively reviewed by Jarosiska and Rdiger.101

Two such approaches specifically target the polyQ region. Bauer et al engineered a fusion molecule consisting of two copies of a polyQ-binding peptide (QBP1) and heat shock-cognate protein 70 (HSC70)-binding motifs to induce chaperone-mediated autophagy.102 Clift et al co-expressed a polyQ-binding antibody (3B5H10) with TRIM21 in an approach that they call Trim-Away, to target mHTT for proteasomal degradation.103 Additionally, Butler et al produced a fusion protein consisting of the scFv-C4 intrabody and a PEST motif to enhance proteasomal degradation of HTT-ex1.104

Several endogenous proteins have been described to enhance the turnover of mHTT, including Praja1 ubiquitin ligase,105 TBK1106 and Blm10/PA200.107 Induction or overexpression of such proteins may represent a therapeutic strategy, although, so far, this notion is only supported by experiments in cellular, Drosophila, and C. elegans models. Additionally, specificity for mHTT has not been shown for any of these three proteins.

Finally, a small molecule that can bind to mHTT-ex1, called GLYN122, has been identified recently. GLYN122 was shown to reduce mHTT-ex1 aggregation in PC12 cells, as well as reducing mHTT in cortex and striatum of R6/2 mice after intraperitoneal injection.108

Next to targeting the pathogenic protein species itself, the production of such proteins can also be inhibited by targeting the HTT mRNA. Many different approaches have been tested to this effect, including ASOs, siRNAs, shRNAs and miRNAs (Table 3). Again, we only focus on those strategies that target HTT-ex1. Broadly speaking, the HTT-ex1 mRNA targeting approaches can be divided into those that target the expanded CAG repeat, and those that target other regions of HTT-ex1. In addition, some other approaches have been described.

Table 3 Overview of Studies That Evaluated Therapeutic Approaches Targeting HTT at the RNA Level

Many studies have tested ASOs or RNAi agents to target the CAG repeat.109122 In general, CAG-targeting confers preference towards the expanded allele, as this allows for binding of multiple molecules per mRNA.111 Only a few studies included in vivo efficacy. Yu et al showed the efficacy of their siRNA in HdhQ150 mice.115 Monteys et al used transgenic mice expressing tagged full-length wtHTT and mHTT, showing preferential silencing of mHTT.118 Datson et al showed the efficacy of their CAG-targeting ASO in R6/2 and Q175 mice,120 an ASO that is now further developed by Vico Therapeutics. Kotowska-Zimmer et al have shown that artificial miRNAs targeting the CAG repeat specifically reduced mHTT in YAC128 mice.122

A number of strategies that target other regions of HTT-ex1 have been described as well.123137 This approach would be expected to lower both wtHTT and mHTT. With the exception of Boado et al and Kordasiewicz et al, who used ASOs, all of these studies utilized RNAi agents. Various groups have demonstrated efficacy of siRNA or shRNA in R6/1, R6/2 and AAV100Q mice.127130 uniQures miRNA therapy has shown target engagement in the widest range of HD animal models, including Hu128/21, Q175 and R6/2 mice, lentiviral rat model and transgenic HD minipigs,123,124,132134,136 as well as a favorable safety profile in toxicity studies in rats and non-human primates.137

A handful of studies described other approaches to HTT RNA-targeting. Rindt et al developed a method to induce trans-splicing, by which mHTT exon 1 is replaced with exogenous wtHTT exon 1 in the mRNA. Thus far, there is only in vitro proof of principle for this approach, and the efficiency is rather low, with 1015% of trans-splicing observed even after extensive optimization.138,139 Batra et al have developed an RNA-targeting Cas9 approach which targets the CAG repeat.140 For HD, there is only in vitro evidence for this approach so far, but a similar approach targeting a CUG (cytosine, uracil, and guanine) repeat was shown to be effective in vivo in myotonic dystrophy type 1 mouse models.141 This platform is being developed by Locanabio.

Finally, some small molecules have been described to bind to either HTT-ex1 or the CAG repeat, most notably furamidine, myricetin and a series of pyridocoumarin derivatives, reviewed elsewhere.12 These compounds have been described to inhibit translation of HTT. However, specificity of such compounds is generally low, thereby increasing the chance of unwanted off-target effects.

Finally, several approaches that target the HTT gene have been described (Table 4).

Table 4 Overview of Studies Targeting the HTT Gene

Transcription can be prevented using zinc finger proteins (ZFPs) targeting the expanded CAG repeat.142144 This approach shows allele-selectivity for the expanded repeat and is currently being developed for the clinic by Sangamo and Takeda. Further, CRISPR-Cas9 genome editing approaches have been developed to either knock out HTT by inducing mutations or excise the region containing the CAG repeat. Several groups have shown in vitro and in vivo proof of principle using single guide RNAs directed to HTT-ex1 to induce HTT knockout.145148 Further, using a double guide RNA approach, various groups have shown that it is possible to excise the region containing CAG repeat.149154 The size of this region differs based on the chosen guide RNAs, with the first report by Shin et al deleting a large 44 kb region,149 while the most precise excision was shown by Yang et al and Monteys et al, who deleted only the CAG repeat and small flanking regions.150,151

Several HTT lowering therapies are either already in clinical trials or are close to entering the clinic. These therapies include different therapeutic modalities and mechanisms of action, each with distinct potential efficacy and safety profiles. Only the approaches in clinical trials or performing IND-enabling studies are covered here.

Two of the most advanced programs, the Phase III trial with the non-allele-specific HTT exon 36-targeting ASO tominersen (Roche) and the phase I/II trials with the allele-specific mHTT-associated single nucleotide polymorphism (SNP)-targeting ASOs WVE-120101 and WVE-120102 (Wave Life Sciences) were halted in 2021, as reviewed elsewhere.155 Roche plans to design a new Phase II study with tominersen, for younger adult patients with lower disease burden (https://ir.ionispharma.com/news-releases/news-release-details/ionis-partner-evaluate-tominersen-huntingtons-disease-new-phase). Wave Life Sciences has now initiated a new trial with their novel product WVE-003, which targets another SNP and has improved chemistry (clinicaltrials.gov NCT05032196). These ASOs are administered repeatedly through intrathecal administration, which may explain some of the adverse events observed with tominersen, which was more pronounced in the cohort receiving more frequent administration.155 Neither drug is expected to affect HTT-ex1 formation or RNA-mediated toxicity.

Novartis and PTC Therapeutics both have initiated Phase 2 clinical trials for their splicing modulators Branaplam (NCT05111249) and PTC518 (NCT05358717). These small molecules induce the inclusion of a pseudoexon between HTT exons 49 and 50, which leads to a premature stop codon and subsequent nonsense-mediated decay.156,157 One of the main advantages is that these small molecules can be administered orally. Furthermore, the mechanism of action targets the pre-mRNA and is therefore quite upstream in the molecular pathology. However, this approach is not specific for the mutant allele and, as it targets a downstream exon, is also not expected to affect HTT-ex1 production or toxic RNA gain-of-function.

In a more indirect fashion, metformin has been shown to reduce translation of HTT through interacting with the MID1/PP2A/mTOR protein complex.158 Interestingly, the effect of metformin was found to be specific for mHTT and to also impact HTT-ex1 protein formation. The drug can be administered orally, and as it is already in clinical use for the treatment of diabetes, its safety profile has already been well established. Metformin is currently being tested for the treatment of HD in a phase III clinical trial to establish its potential as a treatment for HD (NCT04826692). Although it has been shown to reduce HTT levels, RNA-mediated toxicity is not expected to be targeted by its mechanism of action.

There are no therapies that target HTT-ex1 exclusively, but some therapies target HTT-ex1 in addition to the full-length HTT. The most advanced is uniQures gene therapy AMT-130, which is currently being tested in phase I/II clinical trials (NCT04120493 and NCT05243017). AMT-130 is an AAV5-delivered miRNA which is administered through a one-time intrastriatal injection. This therapy is not allele-selective, and its effect on RNA-mediated toxicity has not yet been established.

Several other HTT-ex1 targeting candidates are close to entering clinical trials, including Galyan Bios HTT-ex1 binding small molecule GLYN122 and Vybions INT41 intrabody. These therapeutic candidates target the protein and are therefore not expected to impact RNA-mediated toxicity. According to the companies websites, both are performing IND-enabling studies, although their target date to enter the clinic is not clear (https://www.galyan.bio/pipeline, https://www.vybion.com/?page=product_pipeline).

Likewise, Vico Therapeutics received FDA orphan drug designation for their CAG-targeting ASO in July 2021 and is expected to start clinical trials soon (https://vicotx.com/pipeline/). Takeda and Sangamo are further developing their ZFP approach targeting the CAG repeat (https://www.sangamo.com/programs/). Both approaches preferentially target mHTT and as they act on the (pre-)mRNA and on transcription, respectively, these drug candidates may also have a beneficial effect on RNA-mediated toxicity.

Although all the approaches mentioned, as well as others in earlier phases of development, aim to reduce HTT levels, their mechanism of action is different and not all pathways related to HTT toxicity will be engaged. The relative contribution of each pathway is a matter of debate and is likely to depend on many factors, including age, tissue and cell type. Several of the described mechanisms of N-terminal HTT fragment production, including calpain cleavage and premature polyadenylation, have been shown to correlate with repeat length. This is also the case with HTT-ex1 formation through aberrant splicing. Therefore, it may be expected that as the repeat gets longer over time due to somatic instability, the contribution of these mechanisms will increase. Nonetheless, the broad molecular pathology of HD would likely benefit most from an intervention that acts as far upstream as possible, ie, on the DNA or the RNA level.

For an approach to be successful in disease modification, next to efficiency, adequate safety is key. Safety issues can arise from intrinsic characteristics of the therapeutic modality itself (eg, chemistry, properties of the therapeutic vector, and need of chronic administration), which are not covered in this review. The mechanism of action of the approach can also have different safety risks. Very specific approaches, with a well-understood mechanism, and with low to no interactions with other processes and molecules other than those related to HTT toxicity, would be preferred.

Multiple different approaches are running head-to-head. The small molecule splicing modulators are among the most elegant in terms of delivery, as these are capable of crossing the bloodbrain barrier and can therefore be administered orally. However, these small molecules are not specific for mHTT or even solely for HTT, and long-term studies are needed to determine the safety profile. Furthermore, these splicing modulators are expected to affect neither aberrant splicing of HTT-ex1 nor toxic RNA gain-of-function effects. ASOs and siRNAs have a less favorable distribution and need to be administered locally, although novel chemistries, such as peptide nucleic acids and di-siRNAs, have shown more promising biodistribution and may allow for systemic administration. These synthetic oligonucleotides are active for a limited amount of time, and therefore need to be readministered frequently. CAG-targeting ASOs are expected to not only reduce HTT and HTT-ex1 protein gain-of-function but also to alleviate RNA-mediated toxicity; however, non-specific effects on other genes containing CAG repeats may be difficult to overcome. Finally, the gene therapy approaches utilize AAVs to deliver their cargo. The current generation of AAVs is not sufficiently capable of crossing the bloodbrain barrier and therefore still needs to be administered locally, although efforts are ongoing to identify novel capsids that could be administered in a less invasive manner, eg, Goertsen et al.159 Because most cells that are targeted in HD are non-dividing, a more invasive route of administration is, however, less of an issue, as the therapy would only need to be administered once. uniQures miRNA-based strategy would reduce toxic protein gain-of-function, whereas Takeda and Sangamos ZFP approach targets DNA and thereby acts upstream of mHTT transcription, which would improve both toxic protein- and RNA gain-of-function; yet, as the mechanism of action of this approach involves direct targeting of the repeat, off-target effects may be an issue. Pre-clinically, gene editing approaches using CRISPR-Cas are being explored. However, long-term studies will need to show the safety profiles of such approaches.

To maximize therapeutic efficacy, future research will need to point out whether it may be advantageous to combine various therapeutic strategies with different modes of action. Further, it is likely that any therapeutic approach will benefit from as early intervention as possible. To this end, excellent safety profiles and good biomarkers of both safety and efficacy will be key.160

In summary, we have reviewed the production of N-terminal HTT protein fragments, their role in HD pathology, as well as therapeutic approaches to target these toxic species. Extensive research into HD continues to deepen our understanding of the broad molecular mechanisms leading to disease. With the increasing understanding of the pathological mechanisms associated with mHTT, several different therapeutic approaches are being developed, which will hopefully lead, in the near future, to halting or modification of this devastating disease.

We thank our uniQure colleagues who provided a critical review of the manuscript.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

LB, ME and AV are employees of, and may own stock/options in, uniQure biopharma B.V. In addition, Dr Astrid Valls has a patent WO2021053018 issued to UNIQURE IP B.V. The authors report no other conflicts of interest in this work.

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Emerging Therapies for Huntington's Disease Focus on N-T | BTT - Dove Medical Press

Recommendation and review posted by Bethany Smith

There are over 6 billion letters, or nucleotides, of DNA in the genome. These contain all the information needed to create an individual organism. Certain sequences of DNA, called genes, contain instructions for making proteins that determine everything about how we look and how we function. We expect there to be some differences in those sequences that lead to differences in individual humans, but sometimes these instructions have significant mutations, or changes, that can lead to serious diseases such as cancer.

Imagine having to figure out which changes in which sequences in that long string of 6 billion letters are important for targeting treatments for diseases. And, once you identify some of those important genes, how do you fix those mutations?

A game-changing discovery in 2012 of a system called CRISPR has triggered a revolution in biomedical breakthroughs over the last decade. Scientists can use it to target, edit, modify and regulate genes and put any enzyme or protein they want at any location in the genome. This allows them to find new treatment targets and understand how different genes affect cells in a way that was previously impossible.

But how do we apply CRISPR to understanding cancer? We spoke with Traver Hart, Ph.D., associate professor in Bioinformatics and Computational Biology, to learn more about CRISPR and how it could be used to advance cancer treatment.

What is CRISPR?

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Thats a mouthful, so scientists refer to it as simply CRISPR. These are repeated sequences in the genetic code that were first found in bacteria and were later found to be part of a novel bacterial adaptive immune system against phages, which are viruses that attack bacteria.

This system combines the CRISPR DNA sequences and a set of Cas (CRISPR associated) proteins to identify and destroy invading viral DNA. It also embeds a sample of that viral DNA between these CRISPR sequences so that it can easily recognize and attack the same virus in the future. Thanks to this unexpected discovery in E. coli bacteria, scientists can now harness this method and use it in a similar way within human cells.

How does CRISPR work?

The main part of the CRISPR system is the Cas endonuclease, the Cas protein that cuts DNA strands. These Cas proteins can be programmed to find a 17- to 24-letter sequence by attaching a guide RNA that uniquely matches the specific DNA target. Its similar to a key matching a lock. Researchers have a large library of guide RNAs available that can match certain parts of different genes in the human genome.

Once CRISPR is added to a cell, it searches for and binds to that matching target sequence in the DNA, and the attached Cas protein gets activated to do what scientists have asked it to do. Some Cas proteins such as Cas9 can cut or break the DNA. This is the original protein that was found in bacteria. Others have been engineered to turn a gene on or off without having to cut it. This allows researchers to find out more about what happens if cells make too much (upregulation) or too little (downregulation) of a certain protein and how that can affect the outcome of a cell.

How do we use CRISPR to study cancer in human cells?

For the past several decades, studies have been done in yeast cells and other model organisms where scientists can efficiently edit the genome. The discovery of CRISPR has been instrumental in changing that.

We can edit the genome directly in human cells with unprecedented ease thanks to CRISPR.

Once CRISPR cuts the target DNA, it gets repaired or replaced with a different sequence. Scientists use this method to knock out human genes in cancer cells and identify which of those genes are essential for the growth of tumor cells without harming normal cells. This allows us to nominate gene candidates for drug targets that can be very highly tumor-specific. My lab is trying to find better ways to kill tumor cells by disabling multiple genes at a time using a different Cas protein called Cas12a. This gives us more insight into how different genes and proteins work together in tumor cells to promote cancer progression.

A recent study by Yohei Yoshihama, Ph.D., and Ronald Depinho, M.D., used CRISPR to screen cancer cells and identify a protein called JMJD1C as a candidate target in castration-resistant prostate cancer. Another study by Chao Wang, Ph.D. and Junjie Chen, Ph.D., used CRISPR to screen human cancer cells growing in mouse models and discovered a protein named KIRREL, which was shown to be important for tumor suppression.

Can CRISPR fix genes in people?

While the idea of being able to fix bad genes to cure diseases is a worthy pursuit, science isnt at the point to be able to safely and effectively do so yet. Researchers are looking at how to use CRISPR to correct the genetic defects that cause beta-thalassemia and sickle cell anemia, diseases that affect the amount of hemoglobin in the body and cause patients to require constant blood transfusions. If approved, this type of therapy, called exa-cell, would become the first CRISPR-based medical treatment, which is incredibly exciting.

Whats next for CRISPR?

The possibilities are endless for the information that can be gained from using CRISPR systems and, just 10 years in, scientists have only scratched the surface. Newer Cas proteins and other enzymes are being studied, and there are still questions about how to make CRISPR more specific so that it doesnt accidentally have unintended targets.

Here at MD Anderson, our use of CRISPR continues to lead to a better understanding of how cancer cells function and helps uncover many ways to target individual treatments specific to certain tumors that will, hopefully, one day, achieve our goal to end cancer.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.

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What is CRISPR? - MD Anderson Cancer Center

Recommendation and review posted by Bethany Smith

1. CRISPR infusion eliminates swelling in those with rare genetic disease  Science
2. Intellia Investors Are Dumping Stock on News of Crispr Gene-Editing Success  Barron's
3. Intellia's gene editing therapies both post early successes as evidence grows for CRISPR potential  FierceBiotech
4. Intellia says CRISPR treatment safely corrects DNA of six patients with rare disease  STAT
5. Intellia offers first look at CRISPR drug for rare swelling disorder  BioPharma Dive
6. View Full Coverage on Google News

More here:
CRISPR infusion eliminates swelling in those with rare genetic disease - Science

Recommendation and review posted by Bethany Smith

The move comes at a crucial time for the nearly nine-year-old company, which is on the cusp of asking regulators to approve its first therapy for two genetic blood conditions. Crispr is a pioneer in developing therapies based on the experimental CRISPR gene editing technology, which can make precise changes to DNA. The company, which is valued at more than $5.5 billion, also has earlier-stage programs in treatments for cancer, cardiovascular diseases, diabetes, and neurological conditions.

As were growing and getting more programs into the clinic and ultimately to commercialization, we need more space, said Kulkarni, who has led the company since 2017.

Crisprs new building sits near the southwestern edge of Bostons Seaport, a neighborhood that is a burgeoning new hub for biotech companies looking for an alternative to the increasingly expensive and crowded Kendall Square.

Traditionally, there was a dogma that if youre a biotech company you needed to be in Cambridge, Kulkarni said. But the growing number of biotech firms based there, along with big pharma firms such as AstraZeneca and Bayer opening labs in Cambridge, has made affordable lab space harder to come by.

Only 2.2 percent of the roughly 13 million square feet of lab space in Cambridge was vacant in the second quarter of this year, compared with 13 percent of the nearly 3.8 million square feet of lab space in Boston, according to a market report from the real estate firm Newmark. The average asking price for renting lab space in Boston was about $9 cheaper per square foot as well $105 in Boston versus $114 in Cambridge.

Several drug companies have announced plans this year for new labs in the Seaport, including Boston-based Vertex Pharmaceuticals, the French firm Servier Pharmaceuticals, and the Indianapolis-based Eli Lilly & Co.

The Seaport is really emerging as a vibrant area, Kulkarni said.

A recent report from the Massachusetts Biotechnology Council showed that a slight majority of venture capital money raised by biotech startups in the first half of this year went to firms based outside of Cambridge a reversal from the year prior. Nearly 30 percent of those funds more than $1.5 billion went to startups in Boston.

The number of biotech firms planting roots south of the Charles River is likely to continue. According to Newmark, theres 4.3 million square feet of lab space under construction in Boston largely in the Seaport compared to 2 million square feet under construction in Cambridge.

Kulkarni would not disclose specifics on how much the new building cost, but he said it is more cost-efficient to be in the Seaport. The company spent $241.4 million on research and development expenses in the first half of this year, a 58 percent increase from the first half of 2021, according to the firms quarterly financial statements. Some of these expenses were related to the new building.

The building includes a publicly accessible ground floor with a caf, meeting space, and a thruway to West Second Street. The building was built by Breakthrough Properties, through a joint venture with Tishman Speyer and Bellco Capital.

The firms corporate headquarters will remain in Switzerland, where it was founded. We continue to do business development deals out of there. Its where we started and weve maintained our roots there, Kulkarni said. The firm also has employees at a manufacturing facility in Framingham.

Crisprs most advanced program is a one-time treatment for the genetic blood conditions sickle cell disease and beta-thalassemia. The experimental approach is boosting levels of the crucial blood protein hemoglobin in these patients, and the results from clinical trials look promising so far. Thanks to the genetic fix, people with sickle cell disease are experiencing fewer pain crises and people with beta-thalassemia are requiring fewer blood transfusions to stay healthy.

Crispr plans to submit the therapy, which it is developing with Boston-based Vertex Pharmaceuticals, to European regulators by the end of the year, and potentially to the FDA around the same time or soon after. If approved, it will likely become the first commercial CRISPR therapy.

If someone had said 10 years ago that this new technology is going to be an approved medicine in 10 years, people would have laughed you out of the room. But today its almost a reality, Kulkarni said. And it could be a curative medicine for patients.

Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter @RLCscienceboss.

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Crispr Therapeutics becomes the latest biotech to open in the Seaport - The Boston Globe

Recommendation and review posted by Bethany Smith

BOSTON--(BUSINESS WIRE)--Carver Biosciences, Inc., a biotech company focused on the development of CRISPR/Cas13 antivirals, today announced the closure of a seed round of funding, led by Khosla Ventures.

Carver is focused on using the bacterially derived RNA-directed RNase Cas13 to target respiratory viruses.

The company was founded in 2021 by Dr. Cameron Myhrvold, Assistant Professor at Princeton University. Dr. Myhrvold has worked on developing Cas13-based technologies for studying viral host RNAs since 2016, the year the protein was first discovered. Dr. Walter Strapps joined as co-founder and CEO in February of 2022. Dr. Myhrvold will serve as the chair of Carvers Scientific Advisory Board.

Cas13 opens up a whole new world of possibilities for targeting RNA, much like Cas9 did for targeting DNA," said Dr. Myhrvold. Im particularly excited about using Cas13 to treat viral infections, as the vast majority of viruses dont have FDA-approved therapies or vaccines.

Dr. Strapps is an experienced biotech executive, most recently serving as Chief Scientific Officer at Gemini Therapeutics, a dry age related macular degeneration-focused biotechnology company. Prior to that Dr. Strapps has held various roles leading research efforts in oligonucleotide-based therapeutics, including at Sirna Therapeutics, Merck & Co., Inc and Intellia Therapeutics.

Im very excited by the potential of Cas13 to treat patients infected with respiratory viruses. Cas13 provides us with a programmable platform to treat various existing viruses and to rapidly respond to new viruses as they occur, said Dr. Strapps. Having helped build several therapeutic oligo platforms before, Im thrilled to bring that experience to a new CRISPR protein.

We invest in companies early that are bold and have the ability to make a large impact on society, said Alex Morgan, partner at Khosla Ventures. The major respiratory viruses with great impact on human health are RNA based and include respiratory syncytial virus, influenza virus, parainfluenza virus, metapneumovirus, rhinovirus, and something everyone can appreciate today, coronavirus. The ability to have a programmable therapy that can respond to newly emergent strains in a highly targeted way would revolutionize our approach to infectious disease, from the common cold to some of the major infectious causes of mortality. This team has a unique set of expertise that can hopefully unlock this potential.

Carver will use the seed funding to conduct initial proof of concept Cas13 experiments in cells and in models of disease at their laboratories in Boston and with CRO partners. Cas13 acts by using sequence specific targeting of mRNA to cleave and specifically degrade the targeted RNA. Similar to Cas9 which targets DNA, Cas13 is part of a bacterial immune system that can be used in mammalian cells.

About Carver Biosciences, Inc.

Carver is a Boston, MA-based gene therapy company developing CRISPR-based therapies for RNA viruses that infect humans. Carvers approach is a programmable, platform technology that could offer a generalizable solution for treating many viruses, as targeting is dictated by a guide RNA sequence. The companys underlying technology was developed by co-founder Dr. Cameron Myhrvold. For additional information, please visit http://www.carver.bio.

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Carver Biosciences Launches with Seed Financing to Advance CRISPR/Cas13-based Technologies - Business Wire

Recommendation and review posted by Bethany Smith

Newswise Montana BioAgriculture Inc. is to develop commercial product for wheat stem sawfly:it is now time to CRISPR edit and play with wheat stem sawfly gene and regulatory elements to develop a product for farmers said Dr. Hikmet Budak, Chief Science Officer.

Newswise Insects, diseases, and abiotic stressors cause losses of millions of tons of wheat and cost farmers $100s of millions each year. Solutions can come from understanding and working with interactions between naturally occurring fungi and plants in the common agroecology of US and Canadian wheat growing areas. MBA are working to develop biological solutions to cross border problems affecting North American farmers and global food security.

The wheat stem sawfly, WSS, is the number one insect pest of wheat in North America. There are no effective insecticides. The larvae which cause the damage live their life cycle protected inside the wheat stem. Solid stem wheat varieties can limit damage however lower yields than conventional varieties. WSS apparently first adapted from native grasses to infest spring wheat in North Central Montana spreading into North Dakota and into Canadian prairie provinces. WSS has now adapted to winter wheat, expanding east and south in the US. Our recent forum (International Virtual Wheat Stem Sawfly Forum:Farmer'sVoiceshttps://www.linkedin.com/feed/update/urn:li:activity:6906012389427290112/v) in June, 2022 declared that biopesticide and other products are necessary to control WSS.

Montana BioAgriculture (MT BioAg), has been working on WSS using interdisciplinary tools. It has received two large grants from the US Department of Agriculture to (i) develop a fungus which induces tolerance to drought in wheat and barley, and (ii) use genomics tools to fight against wheat stem sawfly, a major problem in great plains. MT BioAg licensed the fungus to develop as a commercial product.These awards is a major boost to Mt BioAgs work to develop integrated, biological solutions for farmers to reduce losses in grain yield from drought, insects and diseases. Noted by Cliff Bradley MT BioAg president. One of the awards from USDA to evaluate fungi to control wheat stem sawfly and Fusarium head blight (FHB), the most important insect and disease of wheat in Montana. MBA licensed use of fugal stains originally isolated from wheat in Montana by scientist with the USDA Agricultural Research Service. These fungi are natural pathogens of the WSS and are endophytes, that is the fungi colonize the stem without causing damage to the wheat. The fungi infect and kill the WSS larvae inside the stem. Dr. Hikmet Budak, Chief Science officer at MT BioAg said, these projects will utilize new genomics tools in combination with speed breeding. This has been further helping us to CRISPR edit gene(s) to control Wheat Stem Sawfly, FHB and drought stress. With these USDA grants and funds from the Montana Department of Commerce program, MT BioAg has been working on developing production and delivery systems needed to bring these naturally occurring fungi to commercial use. This could lead to higher incomes for grain growers, better nutrition for world populations and new wheat and barley varieties. The research and new findings especially small RNAs (microRNAs, LncRNA) targeting wheat stem sawfly gene and metabolites also offer immense potential for our breeding program to create new discoveries when it comes to advancing global food security." Montana BioAg. Inc., Chief Science Officer said.

Continued here:
CRISPR Editing Wheat Stem Sawfly Genes and Small RNAs. - Newswise

Recommendation and review posted by Bethany Smith

NEW YORK GenScript and Ireland's Avectas said on Tuesday that they're partnering to develop a non-viral cell therapy manufacturing process.

Under the terms of the agreement, their research teams will apply Avectas' Solupore technology to permeabilize target cell membranesto deliver GenScript's GenCRISPR single guide RNA, CRISPR-Cas9 protein, and GenExact single-stranded DNA homology-directed repair templates.

"By combining Avectas' cell engineering technology and know-how with GenScript's expertise in synthetic long oligo production, the partnership aims to demonstrate a novel and efficient solution for cell therapy manufacturing and to improve editing efficiency and cell viability over traditional delivery methods," the firms said in a statement.

"We expect this method will provide our customers with more complete solutions for efficient gene editing using our GenCRISPR sgRNA and ss/dsDNA HDR templates," Ray Chen, president of GenScriptUSALife Science Group, added.

GenScript, a Piscataway, New Jersey-based synthetic DNAmaker, is listed on the Hong Kong Stock Exchange. In May 2021, the firm licensedthe ERS Genomics CRISPR-Cas9 patent portfolio, based on IP held by Emmanuelle Charpentier, one of the pioneers of CRISPR genome editing.

Avectas offers Solupore, a cell engineering technology that delivers payloads to cells by diffusion across a permeabilized membrane.

See the original post here:
GenScript, Avectas Partner on Cell Therapy Manufacturing - GenomeWeb

Recommendation and review posted by Bethany Smith

Portfolio manager Cathie Wood is known for having an aggressive appetite for risk when it comes to the investments she makes in her exchange-traded fund, the ARK Innovation ETF (ARKK -2.47%). Between its stakes in biotech companies with no products on the market and in rising stars like Tesla, its holdings are often in long shots that have the potential to be transformative for their industries or for the world.

On that note, there are two promising -- but speculative -- biotechnology businesses in the ARK portfolio that investors might be interested in if they're patient enough to hold onto their shares for a few years before seeing major returns. Over the next five years, Wood's thesis for both will be tested, so people who buy shares now could join in her eventual profits -- or her losses, which have been substantial for both stocks over the last 12 months.

CRISPR Therapeutics (CRSP 1.90%) is a gene-editing biotech that is working to develop cures for hereditary conditions including sickle cell disease and beta-thalassemia. Before the end of 2022, it expects to ask regulators at the Food and Drug Administration to approve the gene therapy exa-cel, which it claims can functionally cure both diseases. That means sometime in 2023, it could be realizing revenue from sales of its treatments for the first time ever, which will be a major catalyst for the stock.

But CRISPR's true potential actually lies beyond exa-cel. It's also investigating a handful of candidates as off-the-shelf immunotherapies that could treat different cancers, among them lymphoma. The off-the-shelf aspect is what differentiates these programs from the immunotherapies in development by most other companies, and it's also the most exciting thing about CRISPR.

A common problem with sophisticated cell therapies made using genetic engineering is that the patient's body may reject the cell therapy upon infusion. To get around that issue, biopharmas use each patient's own cells as the starting material to manufacture their specific therapy. That's effective, but it's also tremendously expensive because of the costs involved with drawing a sample, shipping it to a manufacturing site, processing it to make a single person's therapy, and then shipping it back to be infused into the patient.

What CRISPR hopes to do is produce non-personalized immunotherapies that don't trigger rejection. If it succeeds, its treatments will be far more scalable to manufacture, far more profitable to sell, and maybe even more effective than those produced by its competitors. That possibility is exactly what Wood is betting on with her investment, but it's almost certain to take a bit longer than a year or two to come to fruition because of how ambitious the goal is.

If you're willing to take a risk that CRISPR won't ever be able to figure it out for the chances of outsized rewards if it does, this is a good stock to buy.

Intellia Therapeutics (NTLA -1.48%) also plans to use advanced gene-editing techniques to treat people's genetic diseases. Like CRISPR Therapeutics, it doesn't have any revenue outside of what it makes from collaborations -- and that only totaled around $33 million in 2021. In terms of its pipeline, it has an early-stage program for sickle cell disease, and other early-stage programs aiming to address transthyretin amyloidosis, a rare hereditary liver disease.

Excitingly, its therapies for those conditions could be curative, though management is careful to remind investors that those treatments could still deliver much-needed relief to patients for long periods without being complete cures, technically speaking. But it isn't anywhere close to commercializing any of its therapies, so it's definitely a stock you'll need to hold onto for at least three or four years before it has the possibility of delivering major returns.

Furthermore, Intellia is developing capabilities similar to CRISPR's with regard to off-the-shelf immunotherapies, though CRISPR's are further advanced. It's pretty clear that Wood bought into Intellia to diversify her bet on easily scalable immunotherapies and give herself two opportunities to succeed. It might make sense for you to do the same if you're looking to hedge your other gene-editing stock plays.

Alex Carchidi has no position in any of the stocks mentioned. The Motley Fool has positions in and recommends CRISPR Therapeutics, Intellia Therapeutics, and Tesla. The Motley Fool has a disclosure policy.

Read more from the original source:
2 Risky Cathie Wood Growth Stocks to Buy and Hold for 5 Years - The Motley Fool

Recommendation and review posted by Bethany Smith

New Jersey, United States, Sept. 18, 2022 /DigitalJournal/ The mRNA Vaccines & Therapeutics Market research report provides all the information related to the industry. It gives the markets outlook by giving authentic data to its client which helps to make essential decisions. It gives an overview of the market which includes its definition, applications and developments, and technology. This mRNA Vaccines & Therapeutics market research report tracks all the recent developments and innovations in the market. It gives the data regarding the obstacles while establishing the business and guides to overcome the upcoming challenges and obstacles.

mRNA vaccines work by introducing a piece of mRNA that matches a viral protein, usually a small piece of a protein found on the outer membrane of the virus. Using this mRNA pattern, the cells produce the viral protein. RNA-based therapies have attracted a lot of attention in recent years due to their high potential in treating chronic diseases. Additionally, in terms of production, distribution and safety, RNA vaccines offer a number of advantages over DNA vaccines. They have also shown promise in human clinical studies, increasing the demand for mRNA-based vaccines and therapeutics.

Get the PDF Sample Copy (Including FULL TOC, Graphs, and Tables) of this report @:

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Competitive landscape:

This mRNA Vaccines & Therapeutics research report throws light on the major market players thriving in the market; it tracks their business strategies, financial status, and upcoming products.

Some of the Top companies Influencing this Market include:CRISPR Therapeutics, Precision NanoSystems, In-Cell-Art, GlaxoSmithKline Vaccines, ETheRNA immunotherapies, Roche Custom Biotech, PhaseRx, BioNTech, MaxCyte, Ethris, Kernal Biologics, AstraZeneca, Argos Therapeutics, RaNa Therapeutics, CureVac, Bayer, Intellia Therapeutics, Novartis, Janssen, Boehringer Ingelheim, Moderna Therapeutics,

Market Scenario:

Firstly, this mRNA Vaccines & Therapeutics research report introduces the market by providing an overview that includes definitions, applications, product launches, developments, challenges, and regions. The market is forecasted to reveal strong development by driven consumption in various markets. An analysis of the current market designs and other basic characteristics is provided in the mRNA Vaccines & Therapeutics report.

Regional Coverage:

The region-wise coverage of the market is mentioned in the report, mainly focusing on the regions:

Segmentation Analysis of the market

The market is segmented based on the type, product, end users, raw materials, etc. the segmentation helps to deliver a precise explanation of the market

Market Segmentation: By Type

Standardization Of Cancer Treatment MRNA VaccineIndividualized Cancer Treatment MRNA VaccineInfectious Disease Treatment MRNA VaccineInfection Prevention MRNA Vaccine

Market Segmentation: By Application

HospitalClinicOthers

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An assessment of the market attractiveness about the competition that new players and products are likely to present to older ones has been provided in the publication. The research report also mentions the innovations, new developments, marketing strategies, branding techniques, and products of the key participants in the global mRNA Vaccines & Therapeutics market. To present a clear vision of the market the competitive landscape has been thoroughly analyzed utilizing the value chain analysis. The opportunities and threats present in the future for the key market players have also been emphasized in the publication.

This report aims to provide:

Table of Contents

Global mRNA Vaccines & Therapeutics Market Research Report 2022 2029

Chapter 1 mRNA Vaccines & Therapeutics Market Overview

Chapter 2 Global Economic Impact on Industry

Chapter 3 Global Market Competition by Manufacturers

Chapter 4 Global Production, Revenue (Value) by Region

Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions

Chapter 6 Global Production, Revenue (Value), Price Trend by Type

Chapter 7 Global Market Analysis by Application

Chapter 8 Manufacturing Cost Analysis

Chapter 9 Industrial Chain, Sourcing Strategy and Downstream Buyers

Chapter 10 Marketing Strategy Analysis, Distributors/Traders

Chapter 11 Market Effect Factors Analysis

Chapter 12 Global mRNA Vaccines & Therapeutics Market Forecast

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mRNA Vaccines & Therapeutics Market to Witness Growth Acceleration | CRISPR Therapeutics, Precision NanoSystems, In-Cell-Art - Digital Journal

Recommendation and review posted by Bethany Smith

FRONT PAGE

Indian and Chinese troops complete disengagement in Hot Springs region

Syllabus:

Preliminary Examination:Current events of national and international importance.

Mains Examination:General Studies II: India and its neighbourhood- relations.

Key Points to Ponder:

Whats the ongoing story- Indian and Chinese troops have completed the disengagement process at Patrolling Point-15 in the Gogra-Hot Springs region of eastern Ladakh, sources in the military establishment said on Tuesday.

Know the Background-In May 2020 when China had diverted its troops who had come to the Tibetan plateau region for their annual exercise, towards the Line of Actual Control (LAC) in eastern Ladakh, creating a standoff with India, PP15 and PP17A were two of the four points where the soldiers were eyeball-to-eyeball.

The six-day process had five components-what are they?

What are PP15 and 17A?

For Your Information-PP15 is located in an area known as the Hot Springs, while PP17A is near an area called the Gogra post.

Map Work-Chang Chenmo river, Gogra-Hot Springs, Kongka Pass, Galwan Valley, Depsang Plains, Line of Actual Control, and Charding Nala region

What is the importance of this region for India?

How significant are they for the military?

India-China Relations during Nehruvian Era-Know in detail

The 1962 India-China War-Know the background

India-China Border Dispute- Know the background

What is Line of Actual Control?

Chinas aggressive attitude towards Indo-China Border and What impact can it have on India-China relations?

Changing dynamics in Indo-China relationships-what are the points of irritation in recent scenario?

Jingoism and not pragmatism nowadays dominate bilateral relations of India with her Neighbours -do you think so? Attest your opinion with few examples

Resolving the Sino-Indian imbroglio-How?

Other Important Articles Covering the same topic:

Explained: In India-China border dispute, strategic significance of Hot Springs, Gogra Post

Dealing with China

Disengagement on Line of Actual Control is a welcome start, but normalisation of India-China relations is a long way off

Govt confirms: Delhi to host G20 summit next Sept

Syllabus:

Preliminary Examination:Current events of national and international importance.

Main Examination:General Studies II: Bilateral, regional and global groupings and agreements involving India and/or affecting Indias Interests

Key Points to Ponder:

Whats the ongoing story India will host the G-20 leaders summit in New Delhi on September 9 and 10 in 2023 under its Presidency, the Ministry of External Affairs (MEA) announced Tuesday.

For your Information India will assume the Presidency of the G20 for one year from December 1, 2022, to November 30, 2023, and is expected to host over 200 meetings across the country, beginning in December this year. India, as G20 Presidency, will be inviting Bangladesh, Egypt, Mauritius, Netherlands, Nigeria, Oman, Singapore, Spain and UAE as Guest countries, said the MEA.

Do you Know-During our Presidency, India, Indonesia and Brazil would form the troika. This would be the first time when the troika would consist of three developing countries and emerging economies, providing them a greater voice, said the MEA in a statement.

What is G20?

Know the origin of G20

How G20 Works?

G20 or Group of Twenty-About, Purpose and Member Countries

What is G20 Troika?

G20 Troika and India-Know in detail

Procedure for taking over the G20 presidency-How it is Decided?

G20-Relevance in todays Changing Geopolitical Dynamics?

For Your Information-Collectively, the G20 accounts for 85 per cent of global GDP, 75 per cent of international trade and two-thirds of the world population, making it the premier forum for international economic cooperation. India is currently part of the G20 Troika (current, previous and incoming G20 Presidencies) comprising Indonesia, Italy and India.

Map Work-G20 member Countries

Other Important Articles Covering the same topic:

Explained: What is the G20, of which India becomes president later this year?

GOVT & POLITICS

Amendment for EWS quota is fraud on Constitution, SC told

Syllabus:

Preliminary Examination:Indian Polity and Governance

Main Examination:General Studies II: Government policies and interventions for development in various sectors and issues arising out of their design and implementation

Key Points to Ponder:

Whats the ongoing story-Questioning submissions that 103rd Constitution amendment provides reservation to Economically Weaker Sections (EWS) without any guard rails unlike in the case of reservations for backward classes, where conditions like maintenance of efficiency of administration is prescribed in Article 335 the Supreme Court on Tuesday said the Constitution did not provide for any such guard rails even in the case of reservation for women.

What Supreme Court said about Article 15(3) part of the original Constitution?

Social justice is the first objective of the Constitution and the heart and soul of the Republic-How Constitution of India ensures social justice?

Economically Weaker Sections and Socially Weaker Sections-Compare and Contrast

What is the 103 Amendment in Indian Constitution?

Know the key highlights of the Economically Weaker Sections Reservation-103rd Constitution (Amendment) Act, 2019

What was the Supreme Courts Verdict in Indira Sawhney case 1992?

Supreme Court on EWS Reservation Criteria-Know about it

EWS Reservation-Issues and Challenges

EWS quota: What are the issues fixed by the Supreme Court?

How is EWS status determined under the law?

What is the basis of the challenge to the amendment?

What has been the governments stand in this matter so far?

What is the difference between quota and reservation?

Other Important Articles Covering the same topic:

Explained: Revisiting definition of EWS

List of essential drugs updated; new diabetes, anti-cancer drugs added

Syllabus:

Preliminary Examination:Current events of national and international importance.

Mains Examination: General Studies II: Government policies and interventions for development in various sectors and issues arising out of their design and implementation.

Key Points to Ponder:

Whats the ongoing story-The Union Health Ministry on Tuesday launched the new National List of Essential Medicines (NLEM), expanding the list to include newer therapies for diabetes, such as the medicine Teneligliptin and the insulin Glargine, and also incorporating four more anti-cancer therapies.

For Your Information-The NLEM guides the governments procurement policy and decides the price cap for medicines. The updated list has deleted 26 drugs from the previous one and added 34 drugs, increasing the list to 384 drugs.

What is National List of Essential Medicine (NLEM)?

Do You Know-The NLEM was first formulated in 1996 and was revised in 2003, 2011, and 2015. It takes into account any changing profile of diseases, newer drugs available in the market, and changing treatment protocols. The price of medicines in the list is controlled by the Centre and cannot be changed by companies themselves. Many of these medicines are also available free at government health facilities.

National List of Essential Medicine (NLEM) in India-Know in detail

Who is National Pharmaceutical Pricing Authority (NPPA)?

National Pharmaceutical Pricing Authority (NPPA) and National List of Essential Medicine (NLEM)-Connect the dots

Why National List of Essential Medicine (NLEM) is significant?

Other Important Articles Covering the same topic:

In a first, regulator hikes prices of essential medicines

EXPRESS NETWORK

Cheetah mitras to watch towers, Kuno ready to host African guests

Syllabus:

Preliminary Examination:General issues on Environmental ecology, Bio-diversity and Climate Change

Main Examination:General Studies III: Conservation, environmental pollution and degradation, environmental impact assessment.

Key Points to Ponder:

Whats the ongoing story- Equipped with a small shed for shade and a few trees, a 5030-metre quarantine enclosure is already at Madhya Pradeshs Kuno National Park to host eight cheetahs arriving from Namibia. Prime Minister Narendra Modi will release three cheetahs two male siblings and a female into the enclosure Saturday to launch the re-introduction of the species in India.

Cheetah in India- Background

Who are cheetah mitras?

Extinction of Cheetah from Indian Landscape-know the reasons

What is the Reintroduction of the cheetah in India plan?

How Reintroduction of the cheetah in India plan is executed?

Action Plan for Introduction of Cheetah in India-Important Highlights

Know the difference between cheetah and Leopard and African cheetah and Asiatic cheetah

Know the Difference between Extinct, Extinct in the Wild and Critically Endangered

Supreme Court of India on Translocating Animals

Translocating Animals-Issues and Challenges

View post:
UPSC Key-September 14, 2022: Why you should read 'National List of Essential Medicine' or 'CRISPR Technology' or 'Coastal Regulation Zone' for UPSC...

Recommendation and review posted by Bethany Smith

Biotech companies with few products on the market and red ink on the bottom line may not look like the most attractive investments right now. Equity markets are still down substantially year-to-date, and in this environment investors prefer putting their money in safer stocks.

But for those with a long-term mindset -- and above-average risk tolerance -- relatively small but promising biotech stocks can be compelling options to buy and hold. Here are two biotech stocks to consider buying that could make investors richer in time: Axsome Therapeutics (AXSM -2.56%)and CRISPR Therapeutics (CRSP 1.90%).

AXSM data by YCharts

Axsome Therapeutics is fresh off an important regulatory milestone. In August, The company's therapy for major depressive disorder (MDD), Auvelity, earned approval from the U.S. Food and Drug Administration (FDA). Auvelity took a while to finally earn the green light due to deficiencies in Axsome's application.But now that it's ready to hit the market, it could become highly successful.

The number of people with depressive symptoms increased threefold at the start of the pandemic, a trend that has persisted. As of 2021, more than 80 million people in the U.S. experienced symptoms of depression. In clinical trials, patients taking Auvelity saw substantial improvement compared to those taking a placebo. What's more, the medicine works relatively fast, with results as early as one week.

The long-term opportunities for this medicine are exciting, especially considering potential label expansions. Axsome recently started a phase 3 clinical trial for Auvelity in treating Alzheimer's disease (AD) agitation. Patients suffering from agitation show signs of emotional distress and physical aggressiveness.There were six million (and growing) AD patients in the U.S. in 2020, and 70% of them suffered from agitation.

Further, there are no approved treatments for this condition, which shows the potential Auvelity has in this area.

Axsome is also running a phase 2 study for Auvelity in smoking cessation treatment. The biotech has other promising programs, including AXS-07, a potential treatment for migraines. The FDA declined to approve AXS-07 earlier this year, but that was due to manufacturing issues, not problems related to the medicine's safety or efficacy. That means there is still an excellent chance AXS-07 will win approval.

Given that more than 37 million patients in the U.S. suffer from acute migraines -- and more than 70% of them are not satisfied with current treatments -- AXS-07's potential also looks strong. Axsome's lineup features Sunosi, a therapy for excessive daytime sleepiness in narcolepsy patients. And in 2023, the company expects to submit an application to the FDA for AXS-14 in treating fibromyalgia (a condition whose symptoms include excessive fatigue and musculoskeletal pain).

Axsome's lineup should become even more impressive within the next few years. The company reported about $8.8 million in sales from Sunosi -- and in total -- during the second quarter. The biotech had no revenue in the second quarter of 2021. Meanwhile, its net loss of $41.4 million was slightly worse than the net loss of $32.3 million reported during the year-ago period.

Axsome Therapeutics is in an excellent position to improve its financial results now that its research efforts are paying off. Expect the biotech company to gain in prominence and size in the coming years.

CRISPR Therapeutics focuses on gene-editing therapies. The company's lead candidate is exa-cel (formerly known as CTX001), a potential treatment for two rare blood diseases: sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT). CRISPR has made some excellent decisions in its effort to market exa-cel. Most of all, it partnered with biotech giant Vertex Pharmaceuticals.

True, CRISPR Therapeutics will have to share the profits associated with exa-cel with its partner on this program if it gets approved. But clinical-stage biotechs are often strapped for cash, and developing innovative therapies isn't cheap. Further, whether an investigational treatment will earn approval is never a sure thing, no matter how promising it looks.

Regardless of whether exa-cel is approved, CRISPR Therapeutics has already collected payments from Vertex in exchange for sharing the rights to the therapy -- the former will receive 40% of the profits and incur 40% of the costs.

The most impressive thing, though, is that exa-cel has been able to produce excellent results in clinical trials to treat these two rare illnesses which have seriously challenged researchers. For instance, 42 of 44 TDT patients treated with the gene-editing therapy were transfusion-free, with follow-up ranging between 1.2 months and 37.2 months.The two that were not yet transfusion-free experienced substantial reductions in transfusion volume.

Vertex Pharmaceuticals and CRISPR Therapeutics plan on filing regulatory applications with the appropriate authorities in the U.S. and Europe by the end of the year. Potential launches could come in late next year. CRISPR also boasts other pipeline candidates. The company's gene-editing platform will get a major vote of confidence if exa-cel earns approval. Of course, it will work wonders for its financial results, too.

The biotech's status as a clinical-stage biotech that is not yet profitable does not inspire much confidence at first glance. But CRISPR Therapeutics could end up being an excellent pick for patient investors.

See the article here:
2 Biotech Stocks That Could Make You Richer - The Motley Fool

Recommendation and review posted by Bethany Smith

In March 2011, a chance meeting between two women changed history without anyone being aware of it. It happened in a cafe in San Juan, Puerto Rico, when the American molecular biologist Jennifer Doudna was introduced to Emmanuelle Charpentier, a French professor of Armenian origin in the same field. They hit it off and, within hours, agreed to a research collaboration. The result, a year later, was the discovery of the CRISPR system: a technology that can be used to edit genes.

Eleven years later, CRISPR is a ubiquitous tool in any molecular biology laboratory in the world, allowing research to be carried out at a speed and cost that were previously unimaginable. Gene editing has also made its way into the experimental treatment of many diseases. CRISPR makes mind-blowing applications possible, such as taking white blood cells from a person, rewriting their genomes to transform them into cancer-killing machines and reinjecting them to fight tumors that havent responded to conventional treatments.

Charpentier and Doudna won the 2020 Nobel Prize in Chemistry for discovering CRISPR. Charpentier, 53, made her fundamental contribution while searching for a way to kill an implacable enemy: the streptococcus pyogenes bacteria, one of the top 10 causes of deadly infections on the planet. It is known as the flesh-eating bacteria because of the horrible wounds it causes if it gets under the skin and reaches the muscle a type of injury that has been documented since the 5th century, appearing in terrible situations. For instance, it inflicted combatants in the US Civil War and heroin addicts in 1990s San Francisco. This bacteria has even become immune to conventional antibiotics.

The investigation into the molecular mechanisms that this bacterium uses to survive external threats was key to discovering CRISPR. The microbes acted as a kind of bacterial immune system, capable of remembering precise fragments of the virus genome, to then cut the virus DNA. But the genome of a virus has millions of letters arranged one after the other how did these microbes manage to identify the genome of the virus and cut it in the exact place?

A few months before the historic meeting in Puerto Rico, Charpentiers team had discovered an RNA molecule that was essential to guiding a pair of molecular scissors to the exact sequence of the genome of each virus. This was key to putting together all the elements needed to build the new CRISPR gene-editing tool.

Three months ago, CRISPR Therapeutics the company Charpentier founded in 2019 published preliminary results from a clinical trial showing that 15 patients with beta thalassemia a severe type of anemia that requires lifelong reliance on blood transfusions had gone months without needing them after receiving a drug that edited the gene that caused the disease.

In early September, Charpentier traveled to Yerevan, Armenia to be one of the main speakers at the Starmus VI Festival. In her interview with EL PAS, the scientist explains that she is still focused on the same goal as she was years ago: looking for new forms of gene editing to combat antibiotic-resistant infections. These superbugs already kill more people than AIDS, malaria and some cancers. For her, one of the greatest dangers we face is that the basic sciences which require years of hard work are no longer attractive to young people, who will need to invent new treatments and medicines in the future. This interview has been edited for the purposes of clarity and brevity.

Question. Where did your interest in science come from?

Answer. At the age of 15, I was obsessed with monasteries I wanted to be a nun for a while. Thats maybe reflected in my work as a scientist: many hours are spent alone, cut off from the world. This is what I did at the University of Ume, in Sweden. I made the key discovery for CRISPR there, while living in my scientific monastery in northern Sweden. At the same time, I was very interested in detective stories, searching for enigmas.

Q. Do you believe in God?

A. My parents were Catholics, but they belonged to a very modern and up-to-date branch of Catholicism, with working-class priests. I grew up in this environment and practiced, but I havent done it for a long time. For me, believing in God is believing in the good of the human being, the best version of humanity.

Q. Are microbes superior to humans?

A. Probably, yes. Long after we have disappeared from the planet, they will still be here. And lets not forget that they already existed long before we appeared! They have solved key problems in their own way. They know how to communicate, adapt, fight theyre extremely versatile. And were talking about a huge community, with millions of different species and an exciting social life.

Q. Social life?

A. They are very social. We can learn a lot from them. The human body contains more bacterial cells than human cells. And this community partly determines how we react to stimuli, why we get sick, how our metabolism works, even some brain functions. I believe that the challenge for human beings is to adapt to the enormous change that is taking place in the microbial universe. We have seen it with a single microbe: SARS-CoV-2. And we are going to see it with new viruses that are yet to come. Many of them will, in part, be driven by human activities on the planet.

Q. Just four years ago, when you spoke to EL PAS, there were hardly any applications of CRISPR in health. Now, especially after the pandemic, there are more and more. Whats the next big step?

A. In origin, CRISPR is an immune system that allows bacteria to defend themselves against viruses. In the coming years, we must perfect the system and be able to use it in a more personalized way. Its the future the study of microbes can solve some of the biggest problems facing humanity. We can create crops that are more resistant to changes in climate and the environment. But the next big step as is usually the case in science will be totally unexpected.

Q. And what role will CRISPR play in treating disease?

A. This tool could help interfere with human metabolism in a beneficial way, to eliminate the negative effects of common diets in the Western world. These same problems are becoming more and more prevalent in Asia [the developing world], because the populations metabolism is not prepared for this type of diet, with lots of meat and enriched carbohydrates. One of the key ailments in this field would be diabetes, for example. Also obesity and infectious diseases.

Q. You head the Max Planck Institute for the Science of Pathogens (Berlin). One of its goals is to combat antibiotic-resistant infections, which are expected to cause the next pandemic.

A. My lab doesnt have many people. We continue to work in a humble way on the specific mechanisms existing in bacteria, so we can identify therapeutic targets and have new antibiotics ready to combat future infections. The development of antibiotics has stagnated in the last 20 years because the pharmaceutical industry is not interested in developing them. We are now starting to see small biotech companies tackling this challenge. I think it is very important to focus on this.

Q. Dont we already know how resistant bacteria are able to make us sick?

A. There are many different mechanisms. The problem is that, as soon as you create a new antibiotic, the bacteria develop immunity to it. Its important to continue researching in this field, looking for new ways to intervene and have different therapeutic compounds. A vaccine is one thing, but you also need antivirals. You have to have different strategies.

Q. What other future issues are you worried about?

A. Being well-armed against resistant bacteria requires a lot of work, a lot of research time. The efforts of many people in different fields, from biologists to doctors, entrepreneurs and businessmen. But the most indispensable are the basic scientists. With the noise of the world we live in today, we see many scientists who finish their doctorates and abandon research. Young generations cant find their place in the academic world, which has not evolved in 30 years. Meanwhile, everything is moving faster and faster, including business. In the US, you can create a biotech company almost instantly and be successful very quickly.

The basic sciences which rely on public funding are ceasing to be attractive, both in terms of funding and mentality. Young people do not want to wait so many years to see the fruits of their labor. Science is being flooded with politics. The system of scientific publications has been filled with marketing. If it continues like this, it will be a very serious problem. Scientists also teach at universities: they are the teachers of the next generations. Without them, not one, but several generations of brains can be lost.

Q. But more and better science is still being done, right?

A. I believe that fundamental biology and the basic sciences overall are in danger. Science involves isolating yourself and working very hard. You have to be able to read more than two pages at a time and work more than eight or nine hours at a stretch. We now see that young students have more and more trouble concentrating or working long hours.

Q. Do you see a solution to this problem?

A. No. I think we all and especially young people need to ask ourselves what kind of world we want to live in. I think kids in rich countries are going to realize that, if they dont change their attitude, theyll be digging their own graves.

Follow this link:
Dr. Emmanuelle Charpentier: We all need to ask ourselves what kind of world we want to live in - EL PAS USA

Recommendation and review posted by Bethany Smith

ProLynx LLC

SAN FRANCISCO, Sept. 20, 2022 (GLOBE NEWSWIRE) --

ProLynx, Inc., a biotechnology company with a novel platform technology for half-life extension of therapeutics, enabling novel and potentially best-in-class treatments to be developed, today announced that Richard King, MBA, has been appointed as Chief Executive Officer and as a member of the Board of Directors. Additionally, Chris Ehrlich, MBA, has joined the company as a member of the Board of Directors.

As a seasoned executive in the industry with a track record of success in partnering, Richard is an excellent fit forProLynx,saidBill Rutter,a ProLynx Board member. The ProLynx Board looks forward to working with Richard and the executive team to realize the promise of our innovative technology for the betterment of patient and caregiver lives. Additionally, I am delighted to welcome Chris to the Board. His expertise in venture capital, business development and financing strengthen the capabilities of our Board.

Richard King is an accomplished executive with over 35 years of leadership experience in the biotechnology and pharmaceutical industries. He has raised over $1bn in private and public capital, completed multiple business transactions, including the sale of Tercica, Inc., the partnership of AcelRx and Grunenthal regarding a novel pain management system, and the strategic affiliation of CALIBR with the Scripps Research Institute.

I am delighted to join ProLynx at this time, saidRichard King. The ProLynx technology is incredibly unique, enabling half-life extension of proteins, peptides and small molecules. This advancement can make existing medications more effective, better tolerated and require less frequent administration. The ProLynx technology can also be applied to molecules in development that might otherwise never be advanced due to efficacy or toxicity issues, allowing these product candidates to move forward and possibly become life-altering treatments for patients.

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Chris Ehrlich began his career with consulting firm LEK before becoming a business development executive in the pharmaceutical industry. Subsequently he was Managing Director at venture capital firm InterWest, serving on multiple company Boards. He joined Locust Walk, a life sciences transaction firm, where, as Global Head of Biotechnology and Head of Strategic Transactions, he sourced and lead multiple transactions for emerging biopharmaceutical companies.

ProLynx is in a great position with its lead development program in clinical trials to treat various cancers, as well as multiple other programs having demonstrated proof of concept across a variety of disease areas, said Chris Ehrlich. I am delighted to join the Board to help bring this novel half-life extension technology forward to advance treatment options for patients in need.

AboutProLynx

ProLynx is a biotechnology company located in San Francisco, CA, developing proprietary drug delivery technologies for half-life extension of therapeutics. The ProLynx pipeline centers on a long-acting oncology drug, PLX038, in Phase 2 clinical trials, a long-acting interleukin 15, PLX015, for immuno-oncology and a very long-acting C-type natriuretic peptide, PLX138, for achondroplasia, together with several other early-stage programs.

Contact

Richard KingRichard@prolynxinc.com

Read more:
ProLynx appoints Richard King as Chief Executive Officer and Chris Ehrlich as Board Director - Yahoo Finance

Recommendation and review posted by Bethany Smith

As the world gets warmer, the use of power-hungry air conditioning systems is projected to increase significantly, putting a strain on existing power grids and bypassing many locations with little or no reliable electric power. Now, an innovative system developed at MIT offers a way to use passive cooling to preserve food crops and supplement conventional air conditioners in buildings, with no need for power and only a small need for water.

The system, which combines radiative cooling, evaporative cooling, and thermal insulation in a slim package that could resemble existing solar panels, can provide up to about 19 degrees Fahrenheit (9.3 degrees Celsius) of cooling from the ambient temperature, enough to permit safe food storage for about 40 percent longer under very humid conditions. It could triple the safe storage time under dryer conditions.

The findings are reported today in the journal Cell Reports Physical Science, in a paper by MIT postdoc Zhengmao Lu, Arny Leroy PhD 21, professors Jeffrey Grossman and Evelyn Wang, and two others. While more research is needed in order to bring down the cost of one key component of the system, the researchers say that eventually such a system could play a significant role in meeting the cooling needs of many parts of the world where a lack of electricity or water limits the use of conventional cooling systems.

The system cleverly combines previous standalone cooling designs that each provide limited amounts of cooling power, in order to produce significantly more cooling overall enough to help reduce food losses from spoilage in parts of the world that are already suffering from limited food supplies. In recognition of that potential, the research team has been partly supported by MITs Abdul Latif Jameel Water and Food Systems Lab.

This technology combines some of the good features of previous technologies such as evaporative cooling and radiative cooling, Lu says. By using this combination, he says, we show that you can achieve significant food life extension, even in areas where you have high humidity, which limits the capabilities of conventional evaporative or radiative cooling systems.

In places that do have existing air conditioning systems in buildings, the new system could be used to significantly reduce the load on these systems by sending cool water to the hottest part of the system, the condenser. By lowering the condenser temperature, you can effectively increase the air conditioner efficiency, so that way you can potentially save energy, Lu says.

Other groups have also been pursuing passive cooling technologies, he says, but by combining those features in a synergistic way, we are now able to achieve high cooling performance, even in high-humidity areas where previous technology generally cannot perform well.

The system consists of three layers of material, which together provide cooling as water and heat pass through the device. In practice, the device could resemble a conventional solar panel, but instead of putting out electricity, it would directly provide cooling, for example by acting as the roof of a food storage container. Or, it could be used to send chilled water through pipes to cool parts of an existing air conditioning system and improve its efficiency. The only maintenance required is adding water for the evaporation, but the consumption is so low that this need only be done about once every four days in the hottest, driest areas, and only once a month in wetter areas.

The top layer is an aerogel, a material consisting mostly of air enclosed in the cavities of a sponge-like structure made of polyethylene. The material is highly insulating but freely allows both water vapor and infrared radiation to pass through. The evaporation of water (rising up from the layer below) provides some of the cooling power, while the infrared radiation, taking advantage of the extreme transparency of Earths atmosphere at those wavelengths, radiates some of the heat straight up through the air and into space unlike air conditioners, which spew hot air into the immediate surrounding environment.

Below the aerogel is a layer of hydrogel another sponge-like material, but one whose pore spaces filled with water rather than air. Its similar to material currently used commercially for products such as cooling pads or wound dressings. This provides the water source for evaporative cooling, as water vapor forms at its surface and the vapor passes up right through the aerogel layer and out to the environment.

Below that, a mirror-like layer reflects any incoming sunlight that has reached it, sending it back up through the device rather than letting it heat up the materials and thus reducing their thermal load. And the top layer of aerogel, being a good insulator, is also highly solar-reflecting, limiting the amount of solar heating of the device, even under strong direct sunlight.

The novelty here is really just bringing together the radiative cooling feature, the evaporative cooling feature, and also the thermal insulation feature all together in one architecture, Lu explains. The system was tested, using a small version, just 4 inches across, on the rooftop of a building at MIT, proving its effectiveness even during suboptimal weather conditions, Lu says, and achieving 9.3 C of cooling (18.7 F).

The challenge previously was that evaporative materials often do not deal with solar absorption well, Lu says. With these other materials, usually when theyre under the sun, they get heated, so they are unable to get to high cooling power at the ambient temperature.

The aerogel materials properties are a key to the systems overall efficiency, but that material at present is expensive to produce, as it requires special equipment for critical point drying (CPD) to remove solvents slowly from the delicate porous structure without damaging it. The key characteristic that needs to be controlled to provide the desired characteristics is the size of the pores in the aerogel, which is made by mixing the polyethylene material with solvents, allowing it to set like a bowl of Jell-O, and then getting the solvents out of it. The research team is currently exploring ways of either making this drying process more inexpensive, such as by using freeze-drying, or finding alternative materials that can provide the same insulating function at lower cost, such as membranes separated by an air gap.

While the other materials used in the system are readily available and relatively inexpensive, Lu says, the aerogel is the only material thats a product from the lab that requires further development in terms of mass production. And its impossible to predict how long that development might take before this system can be made practical for widespread use, he says.

This work "represents a very interesting and novel system integration approach of passive cooling technologies," says Xiulin Ruan, a professor of mechanical engineering at Purdue University, who was not associated with this research. Ruan adds, "By combining evaporative cooling, radiative cooling, and insulation, it has a better cooling performance and can be effective in a wider range of climates than evaporative cooling or radiative cooling alone. The work could attract significant practical applications, such as in food preservation, if the system can be made at reasonable cost."

The research team included Lenan Zhang of MITs Department of Mechanical Engineering and Jatin Patil of the Department of Materials Science and Engineering.

Read the original here:
Passive cooling system could benefit off-grid locations - MIT News

Recommendation and review posted by Bethany Smith

Anderson, South Carolina--(Newsfile Corp. - September 20, 2022) - JZZ Technologies Inc.'s (OTC Pink: JZZI) ("JZZ" or the "Company")newly created digital marketing division has added 28 million new records to its database for marketing to U.S. healthcare products consumers.

JZZ Technologies, Inc. has acquired marketing data for more than 28 million U.S. healthcare product consumer records as part of its ongoing data acquisition efforts. These new records will be offered to Active Lifestyle Marketing customers as part of the Company's emerging marketing suite of products that includes 30+ million seniors, medical professionals, B2B contacts, 17 million metaverse users and now, 28 million healthcare products consumers.

The deal with a third-party provider requires that JZZ Technologies participate in a structured data sharing plan whereby JZZ and the data provider exchange records.

Email direct marketing is still considered among the most effective forms of digital advertising and the medical consumer segment offers one of the best yields in the industry. According to the digital marketing analysis group Wordstream, healthcare advertisers pay an average cost per click of $3.17 for ads through digital platforms. That compares to the average across all industries which is just $2.32 per click.

Using the comparable models for pricing, JZZ expects that its new record set can potentially generate up to an average of $315,000 per send. That is based on delivering a .5% click rate utilizing the entire new database with a 75% in-box delivery rate. The click rate may be higher or lower depending on individual marketing messages and other factors.

Charles Cardona, CEO of JZZ technologies, Inc. stated, "We will continue to broaden our product selection for Active Lifestyle Digital Media products as possible. The medical products consumers segment is naturally aligned with our audience of adults 55+ and it's a great source for digital income. We plan to focus on this segment as much as possible to maximize our potential for revenue."

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"We are beginning to generate revenue from our database with major digital service providers and that will start to really bear fruit in the next quarter," Cardona adds.

JZZ currently holds data sets for active adults age 55+, medical professionals, veterans, B2B contacts and many other segments. The total database of records owned and/or licensed by JZZ Technologies now equals roughly 70 million records. The Active Lifestyle Marketing division is continuing to segment the targeted data to include specific verticals such as individuals with diabetes, aging issues, and insurance consumers, among others.

About JZZ Technologies, Inc.

JZZ Technologies, Inc. is a diversified technology company engaged in digital media business which includes online media and apps (activelifestylemedia.com), content creation, and digital marketing, targeted to active adults 55+, strategic biotechnology and bioscience related to Human Life Extension and quality of life businesses that support improved quality of life for the aging population. For more information, please visit http://www.jzztechnologies.com.

Press Contacts:JZZ Technologies, Inc.Charles Cardona, CEOccardona@jzztechnologies.com

DISCLAIMER and FORWARD-LOOKING STATEMENTS

Certain statements contained herein are "forward-looking" statements (as such term is defined in the Private Securities Litigation Reform Act of 1995). Because such statements include risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities and Exchange Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended, and such Forward-Looking Statements are intended to be covered by the safe harbors created thereby. Investors are cautioned that all forward-looking statements involve risks and uncertainties. All statements other than statements of historical fact in this announcement are forward-looking statements, including but not limited to the viability of the Company's business plans, the effect of acquisitions on our profitability, the effectiveness, profitability, and the marketability of the Company's products; the Company's ability to protect its proprietary information; general economic and business conditions; and the volatility of the Company's operating results and financial condition. These forward-looking statements involve known and unknown risks and uncertainties and are based on current expectations, assumptions, estimates, and projections about the Company and the industry. The Company undertakes no obligation to update forward-looking statements to reflect subsequent occurring events or circumstances or to changes in its expectations, except as may be required by law. Although the Company believes that the expectations expressed in these forward-looking statements are reasonable, management cannot assure the public that their expectations will turn out to be correct. Investors are cautioned that actual results may differ materially from the anticipated results.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/137718

Link:
JZZ Technologies, Inc. Adds 28 Million Healthcare Products Consumer Records to Its Active Lifestyle Media Marketing Database - Yahoo Finance

Recommendation and review posted by Bethany Smith

NorthStar Earth & Space

NorthStar Earth & Space

NorthStar Earth & Space (NorthStar) and Astroscale announce today, at the 2022 International Astronautical Congress (IAC) in Paris, that they are forming a strategic partnership to further support space sustainability by combining NorthStars precise space-based resident space object tracking with Astroscales enhanced spacecraft navigation and capture capability for on-orbit servicing.

Under this agreement, Astroscale and NorthStar will leverage their respective know-how, expertise, and unique services to highlight their shared commitment to space sustainability. Together, NorthStar and Astroscale will cooperate to demonstrate the benefits of combining precise In-Space Situational Awareness (ISSA) services to support reliable on-orbit servicing in low Earth orbit.

In 2023, NorthStar will launch the first commercial Space Situational Awareness service to deliver higher precision detection, tracking, and coverage for all near-Earth orbital regimes. NorthStars Space Information and Intelligence (Si2) services will serve all satellite operators to better manage their fleets, enhance spaceflight safety, and ensure space sustainability.

Astroscale is advancing its End-of-Life Services, most recently tested during its ELSA-d mission, which successfully magnetically captured its demonstration client spacecraft in August 2021. The latest ELSA-M servicer is in rapid development for launch in 2024 in partnership with OneWeb, the UK Space Agency and the European Space Agency. The state-of-the-art ELSA-M servicer will capture and retire multiple client spacecraft during a single mission. This collaboration will advance specific ISSA services required to support the tracking and capture of the Client spacecraft, as well as provide essential space-safety information about other space objects in orbit. Astroscale will endeavour to partner with NorthStar as a supplier of SSA services for future Astroscale missions.

NorthStar is proud to join forces with Astroscale as part of an essential community that is committed to advancing innovation and commercial services for space sustainability, said Stewart Bain, CEO & Founder of NorthStar Earth & Space. Combining NorthStars space-based coverage with Astroscales impressive on-orbit servicing capabilities is a very powerful response to immediate challenges in all near-Earth orbits

Were delighted to announce this partnership with NorthStar to develop our in-space situational awareness technology and data, said Nick Shave, Managing Director of Astroscale Ltd. We see an opportunity to enhance our spacecraft servicer and client satellite navigation & tracking capability with support from Northstars Space Information and Intelligence Services. Were keen to leverage our Rendezvous and Proximity Operations (RPO) and satellite capture expertise and advance our commercial on-orbit debris removal services with the benefit of both ground derived and in-space data. This is a great partnership that we look forward to harnessing with our forthcoming ELSA-M mission to clean up space and protect our orbital environment for future generations.

About NorthStarNorthStar seeks to empower humanity to preserve our planet through a unique Space and Earth information & intelligence platform using space-based sensors. NorthStar strives to help transform the way governments, industry and institutions assess risk, enforce regulations and make decisions to foster the sustainable development of our earth and space environment.

NorthStars unique space-based commercial Space Situational Awareness services address many of the critical and immediate challenges facing all satellite operators. Striving to see every object in every orbit, NorthStar will deliver more frequent and precise observations of resident space objects than any current system. Through a suite of high-speed decision quality information services derived from its unparalleled coverage, object custody, and enhanced predictive analytics NorthStar generates its Space Information & Intelligence services.

NorthStars investors comprise a global coalition of strategic partners, including Telesystem Space (a co-enterprise of the Sirois family office, Telesystem and the Rogers Family Trust of Canada), the Space Alliance of Europe (Thales Alenia Space and Telespazio), the Government of Quebec, the Government of Canada and the Luxembourg Future Fund. NorthStar Earth & Space head offices are located in Montral, Canada, its U.S. subsidiary, NorthStar Earth & Space Systems, Inc. is headquartered in McLean, Virginia and its European subsidiary, NorthStar Earth & Space Europe S. r.l. is headquartered in Luxembourg.

https://northstar-data.com/

About AstroscaleAstroscale is the first private company with a vision to secure the safe and sustainable development of space for the benefit of future generations, and the leading company dedicated to on-orbit servicing across all orbits.

Founded in 2013, Astroscale is developing innovative and scalable solutions across the spectrum of on-orbit servicing, including in-space situational awareness, end-of-life, and active debris removal and life extension, to create sustainable space systems and mitigate the growing and hazardous build-up of debris in space. Astroscale is also defining business cases and working with government and commercial stakeholders to develop norms, regulations, and incentives for the responsible use of space.

Headquartered in Japan, Astroscale has an international presence with subsidiaries in the United Kingdom, the United States, Israel, and Singapore.

Astroscale is a rapidly expanding venture company, working to advance safe and sustainable growth in space and solve a growing environmental concern.

Find out more at http://www.astroscale.com

The rest is here:
Astroscale and NorthStar Partner to Develop In-Space Technology to Support Space Sustainability - Space Ref

Recommendation and review posted by Bethany Smith

Proactive

Sydney, Sept. 16, 2022 (GLOBE NEWSWIRE) -- Proactive, provider of real-time news and video interviews on growth companies listed in Australia, has covered the following companies:

EQ Resources Ltd (ASX:EQR) has delivered a significant increase in its Mt Carbine ore reserve and a substantial decrease in strip ratio, which improves mine life extension potential for Australias only primary tungsten producer.Click here

Radiopharm Theranostics Ltd (ASX:RAD) shares were trading 9% higher intra-day, at 18 cents, after securing a rare paediatric disease (RPD) designation for its DUNP19 technology for treating osteosarcoma by the US Food & Drug Administration (FDA).Click here

West Wits Mining Ltd (ASX:WWI)s preliminary trade-off studies as part of the Witwatersrand Basin Project (WBP) Project 200 initiative have confirmed the merits of progressing to a further scoping study.Click here

SenSen Networks Ltd (ASX:SNS, OTCQB:SNNSF) has delivered accelerating growth over the 2022 financial year, with operating results reflecting continued investments to support the companys rapid, ongoing vertical and geographic expansion, according to a report by Edison Research.Click here

Anson Resources Ltd (ASX:ASN) has added $50 million to the coffer for its Paradox Lithium Project in Utah, USA after securing binding commitments from institutional and sophisticated investors for a single tranche placement.Click here

Nova Minerals Ltd (ASX:NVA, OTCQB:NVAAF) and its 37%-owned affiliate Snow Lake Lithium have completed a further 20,000 metres of drilling at the Snow Lake Lithium Project in Manitoba, Canada, tripling the amount of drilling data that can be leveraged for an upcoming resource upgrade.Click here

New Century Resources Ltd (ASX:NCZ) has enhanced its board and management skillset with the appointment of senior resource industry professional Robert Cooper as its new managing director and CEO.Click here

Ora Banda Mining Ltd (ASX:OBM) will lose Keith Jones as a member of its board of directors as he plans to retire at the end of the month after more than three years with the company.Click here

Galena Mining Ltd (ASX:G1A) has achieved 83% construction progress as of August 31, 2022 at its Abra Base Metals Mine, situated in the Gascoyne region of Western Australia.Click here

Antipa Minerals Ltd (ASX:AZY) will receive a further $1 million boost to its capital-raising exercise as major shareholder Newcrest Mining Ltd intends to exercise its top-up right to maintain its 9.9% shareholding in the mineral exploration company.Click here

Lanthanein Resources Ltd (ASX:LNR)'s maiden drill campaign at the Lyons rare earths project, which started this week, is partially complete.Click here

ioneer Ltd (ASX:INR, OTC:GSCCF) has successfully completed a Technology System Supply Agreement with Caterpillar, the worlds largest manufacturer of construction and mining equipment and a leader in developing autonomous technology.Click here

Euro Manganese Ltd (ASX:EMN, TSX-V:EMN, OTCQX:EUMNF) has now filed two important instruments in the development of its Chvaletice Manganese Project in the Czech Republic.Click here

Strickland Metals Ltd (ASX:STK) has secured $1.225 million in funding in this latest share purchase plan (SPP), taking the company a step closer to its capital raising goal of $7 million.Click here

Duke Exploration Ltd (ASX:DEX) has received final assays from the reverse circulation (RC) drilling program it started in February at its flagship Bundarra Project.Click here

Story continues

About Proactive

Proactive is a unique tech-enabled platform providing companies globally with a comprehensive investor engagement solution across their business lifecycle.

With six offices on three continents, Proactive works with innovative growth companies quoted on the worlds major stock exchanges, helping executives to engage intelligently with investors.

In 2020, Proactive featured in 809 million search results, our content was viewed over 165 million times and our readers spent over 10 million hours on our websites. Proactive has produced over 300,000 articles and 20,000 executive interviews since it was established in 2006.

For more information on how Proactive can help you make a difference, email us at action@proactiveinvestors.com

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Proactive news headlines including EQ Resources, Radiopharm Theranostics, West Wits Mining and SenSen Networks - Yahoo Finance

Recommendation and review posted by Bethany Smith

VANCOUVER, BCandTORONTO, Sept. 16, 2022 /PRNewswire/ - Agnico Eagle Mines Limited (TSX: AEM) (NYSE: AEM) ("Agnico Eagle") and Teck Resources Limited (TSX: TECK.A) (TSX: TECK.B) (NYSE: TECK) ("Teck") announced today that Agnico Eagle has agreed to subscribe for a 50% interest in Minas de San Nicols, S.A.P.I. de C.V. ("MSN"), a wholly-owned Teck subsidiary which owns the San Nicols copper-zinc development project located in Zacatecas, Mexico (the "Transaction"). As a result of the Transaction, Teck and Agnico Eagle will become 50/50 joint venture partners at San Nicols.

"San Nicols is a high-quality project, located in a leading mining jurisdiction, with high grades, extremely competitive capital intensity, and first quartile costs," said Don Lindsay, President and CEO of Teck. "The opportunity to add the operating and development experience of Agnico Eagle should generate substantial benefits for the project including for all stakeholders throughout the project life cycle."

"This is a unique opportunity to create a long-term partnership between two high quality mining companies working together to de-risk and optimize a world class VMS deposit in a premier mining jurisdiction," added Ammar Al-Joundi, President and CEO of Agnico Eagle. "Agnico Eagle's project development, permitting and construction experience in Mexico, combined with Teck's base metals expertise, operating excellence and marketing leadership, are complementary skillsets and will contribute to the timely and successful development and operation of San Nicols."

Transaction Highlights

San Nicols Project Highlights

San Nicols Study Status

A detailed plan to complete a feasibility study, permitting, and community engagement has been developed, with initial work underway since January 2022. Further, an environmental and social baseline survey, including in-depth archaeological surveys and clearances, was carried out by Teck from 2018 to 2021. Well-developed community engagement and investment programs have resulted in strong support for development from stakeholders near the project and more broadly in Zacatecas.

The feasibility study is expected to be completed early in 2024 with project sanction thereafter subject to receipt of permits.

About the Transaction

Agnico Eagle will subscribe for US$580 million in MSN shares, through a wholly-owned Mexican subsidiary of Agnico Eagle, giving Agnico Eagle a 50% interest in MSN. The subscription proceeds received from Agnico Eagle will be used by MSN to fund the first US$580million of post-closing costs with subsequent funding to be contributed according to each partner's ownership percentage. Agnico Eagle's contributions will be made as study and development costs are incurred there is no up-front payment from Agnico Eagle. The US$580million share subscription implies a notional US$290million acquisition cost to Agnico Eagle for 50% of the San Nicols project plus the contribution by Agnico Eagle of 50% of the first US$580million of project costs for its own account.

Funding requirements beyond this initial subscription amount will be funded by Teck and Agnico Eagle in proportion to their shareholdings in MSN. The shareholders' agreement will include provisions typical in a transaction of this nature, as well as remedies for material breach that include accelerated dilution and forced sale of a defaulting shareholder's ownership interest. For governance purposes, Agnico Eagle will be deemed a 50% shareholder of MSN from closing, regardless of the number of shares that have been issued to Agnico Eagle.

Closing of the Transaction is subject to customary conditions precedent, including receipt of necessary regulatory approvals, and is expected to occur in the first half of 2023.

Additional Information on the San Nicols Project

For further details on the San Nicols project, please refer to the Supplemental Information slides in the Investors section of Teck's website (https://www.teck.com/investors/events-&-presentations/presentations-webcasts/supplemental-information-for-investors).

About Teck

As one of Canada's leading mining companies, Teck is committed to responsible mining and mineral development with major business units focused on copper, zinc, and steelmaking coal, as well as investments in energy assets. Copper, zinc, and high-quality steelmaking coal are required for the transition to a low-carbon world. Headquartered in Vancouver, Canada, Teck's shares are listed on the Toronto Stock Exchange under the symbols TECK.A and TECK.B and the New York Stock Exchange under the symbol TECK. Learn more about Teck atwww.teck.comor follow@TeckResources.

About Agnico Eagle

Agnico Eagle is a senior Canadian gold mining company, producing precious metals from operations in Canada, Australia, Finland, and Mexico. It has a pipeline of high-quality exploration and development projects in these countries as well as in the United States and Colombia. Agnico Eagle is a partner of choice within the mining industry, recognized globally for its leading environmental, social and governance practices. The Company was founded in 1957 and has consistently created value for its shareholders, declaring a cash dividend every year since 1983.

Forward Looking Statements

This news release contains certain forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995 and forward-looking information as defined in the Securities Act (Ontario). Forward-looking statements and information can be identified by statements that certain actions, events or results "could", "may", "might", "should", "will" or "would" be taken, occur or achieved. Forward-looking statements in this news release include statements regarding the expectation that the Transaction will close and the timing of closing; the expectation that the San Nicols project will be developed into production; the expected timing of first production; the estimated mine life; the expectation that there is meaningful mine life extension and regional exploration potential; the expected ownership interests of Teck and Agnico Eagle in the joint venture at any time; the expected production over the first five years of operation; all San Nicols project economics included in this news release, including head grades, average C1 operating costs, development capital cost estimate, payback period and IRR; the expectations as to results of the feasibility study, including development capital cost estimate, payback period and IRR; the statement that the project has been de-risked; and timing of project sanction decision.

Forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause the actual results, performance or achievements of Teck, Agnico Eagle or the joint venture to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Factors that may cause actual results to vary include, but are not limited to, changes in general economic conditions or commodity prices, unanticipated permitting, development or construction issues including delays in receiving permits or other regulatory approvals, or withdrawal or suspension of permits, unanticipated geotechnical conditions or other factors affecting construction plans and budgets including supplier, transportation, logistics or labour issues, adverse weather or natural disaster, community unrest, access issues, failure of plant and equipment, disruption of financial markets, the accuracy of our mineral estimates (including with respect to size, grade and recoverability) and the geological, operations and price assumptions on which these are based, other circumstances interfering with the closing of the Transaction, including an inability to satisfy the conditions to closing, including receipt of any regulatory approvals and failure by Teck or Agnico Eagle to fund as required by the agreements. Economic projections for the San Nicols project are presented on a 100% basis and, except as otherwise noted, assume US$3.50/lbcopper, US$1.15/lbzinc, US$1,550/oz gold, and US$20/oz silver.

Teck and Agnico Eagle caution you that the foregoing list of important factors and assumptions is not exhaustive. Other events or circumstances could cause actual results to differ materially from those estimated or implied by these forward-looking statements. Certain of these risks are described in more detail in the Annual Information Form of Teck and/or Agnico Eagle and in their respective subsequent quarterly report filings with Canadian securities administrators and the US Securities and Exchange Commission. Neither Teck nor Agnico Eagle assumes the obligation to revise or update these forward-looking statements after the date of this news release or to revise them to reflect the occurrence of future unanticipated events, except as maybe required under applicable securities laws.

SOURCE Agnico Eagle Mines Limited

Original post:
Teck and Agnico Eagle Announce Agreement on the San Nicols Copper-Zinc Project located in Zacatecas, Mexico - PR Newswire

Recommendation and review posted by Bethany Smith

Russias cutting-edge war machine, the MiG-31, capable of firing deadly hypersonic missiles, demonstrated its firing capabilities in the upper reaches of the atmosphere.

Russian Su-35 Fighter Demolished Ukrainian Air Defense Radar By Firing Anti-Radiation Missile, Moscow Says

Officials in the Russian Navys Baltic Fleet recently announced that Russian MiG-31 fighter jets practiced missile attacks during maneuvers in the stratosphere on September 13, Russian media Pravda reported. The Baltic fleet is headquartered at Kaliningrad.

The pilots of MiG-31 aircraft practiced flight maneuvers in the stratosphere, trained their skills to escape attacks from mock enemy aircraft and relocate to operational airfields of the region, said the statement from the Baltic Fleet.

In February, EurAsian Times reported that Russia had reportedly stationed a MiG-31K Foxhound fighter jet armed with a Kinzhal hypersonic land-attack missile in Kaliningrad along the Baltic Coast. The deployment was made days before the Russian troops launched their so-called special military operations.

Later, the Russian Ministry of Defense announced on August 18 the deployment of three MiG-31 fighters armed with Kinzhal hypersonic missiles to Chkalovsk airfield in the Kaliningrad Region as part of additional strategic deterrence measures.

According to reports, the three aircraft were moved to the Kaliningrad area for the exercises, where they simulated strikes on mock-up enemy command centers as part of training flights. The flights of the MiG-31 aircraft took place under the cover of Su-27 fighters.

It is pertinent to note that the Baltic region in Eastern Europe has seen hyper-vigilance from Moscow and the West in the aftermath of the invasion. When the Russian invasion began, the US sent its fighter jets to the Baltic for NATOs air policing missions.

MiG-31s are not frequently stationed at Russias Kaliningrad location. Some of the 50 aircraft stationed at the facility are older Su-27 and Su-24 fighters, with some newer Su-30SM and Su-35S jets on the way. According to reports, Iskander missiles are also housed in the enclave.

Besides the MiG-31 fighter jet, Russian reports indicated that the crews of the Eleron and Orlan-10 unmanned aerial vehicles of the Baltic Fleet practiced the tactics to overcome the air defense zone of a mock enemy at the Kaliningrad enclave.

While the MiG-31 drills are significant as they come during a surprising counter-offensive by Ukraine, it is not the first time this mighty warplane conducted exercises in the stratosphere. The MiG-31 had practiced in the stratosphere as early as 2017.

Further, in August 2019, the crews of upgraded MiG-31BM fighter jets held their first-ever dogfight in the stratosphere at an altitude of over 20 kilometers, as previously reported by TASS.

The two-seat MiG-31, known as the Foxhound under its NATO designation, is Russias primary fighter-interceptor aircraft. It has two D-30F6 engines, which help the aircraft have a base range of 1900 miles and a top speed of Mach 3 at high altitudes.

The MiG-31 is equipped with the SBI-16 Zaslon fixed phased array antenna radar, one of the most advanced in the world, to support its long-range and high-altitude air defense duty. The MiG-31 can engage air targets with various long and short-range missile combinations in addition to its Gsh-6-23 23mm gun.

The Russian Defense Ministry announced its plans to fund a MiG-31 Foxhound interceptor modernization and life extension program in July 2020. The MiG-31 can fly at high speeds and low altitudes, thanks to its sleek and aerodynamic body. The aircraft is built to track several targets at high altitudes simultaneously.

Despite Russias claims that it is developing the MiG-41 to replace the MiG-31, there is little evidence that the plane will be operational soon. Therefore, Russia has decided to develop several updated MiG-31 variants that will enable the Foxhound to continue service for many years. The MiG-31BM is the most notable of these.

The MiG-31BM is one of the MiG-31s most potent variants. It is a multipurpose, fast, long-range fighter with the power to destroy air and ground targets.

The MiG-31BM includes upgraded avionics, hands-on-throttle-and-stick (HOTAS) controls, liquid-crystal color multifunction displays (MFDs), a robust onboard computer system, digital data linkages, and phased array radar. It has the capability of intercepting 24 targets at once.

The MiG-31BM was initially intended to carry Kinzhal hypersonic missile, but MiG-31K was later selected as the carrier, according to Russian Defense Minister Sergei Shoigu. MiG-31Ks were used to strike targets early in Russias 2022 invasion of Ukraine with Kinzhals. Only 10 to 20 MiG-31Ks have beenupgradedto fire Kinzhals.

These Russian interceptor fighters have also intercepted NATO spy planes and fighter jets and will potentially continue to be deployed for a long time. In January,China-based Sohu publication had referred to the Russian MiG-31 interceptor fighter as a mysterious killer.

Read more:
Russias MiG-31 Fighter That Fired Hypersonic Missiles On Ukraine Conducted Drills In The Stratosphere - EurAsian Times

Recommendation and review posted by Bethany Smith

New York, Sept. 20, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Space In-Orbit Refueling Market - A Global and Regional Analysis: Focus on Application, End User, Capability, and Country - Analysis and Forecast, 2022-2032" - https://www.reportlinker.com/p06317753/?utm_source=GNW 8 million by 2032 at a compound annual growth rate (CAGR) of 103.85% during the forecast period 2022-2032 (CAGR:2026-2032). The major factor driving the market growth is expected to be the increase in demand for sustainable and reusable space systems.

With the increasing number of satellites going into space, the demand for satellite servicing has been rising.In the future years, refueling capabilities are expected to become a need rather than an option for satellite operators.

Several market players have already started demonstrations and some have been successful. Commercial players are expected to extract the maximum benefit of the space in-orbit refueling technologies.

Market Lifecycle Stage

Space in-orbit refueling has been on the wishlist of satellite operators for decades, however, even though the concepts existed, no company was able to materialize the technology.However, in the past 5 years, multiple established players and startups have entered the market and are now full-fledged working on the refueling capabilities.

Massive amounts of investments are pouring into the industry and multiple collaborations are happening in order to co-develop new technologies.

Over 15 years of research and development on satellite refueling technologies have bought us to a stage where key players are performing successful demonstrations of in-orbit refueling and services in-orbit.Additionally, commercial players with large constellation sizes or heavy communication satellites are expected to adopt the market first.

Following this, government agencies like NASA and ESA are also stepping forward to develop technologies and fund startups in the in-orbit refueling industry.

Applications, such as site earth observation, communication, and navigation, are some of the areas where satellites are expected to be refueled in the coming years. Moreover, newer technologies, such as advanced docking systems, fueling ports, and artificial intelligence software are expected to support the growth of the space in-orbit refueling market over the 2022-2032 forecast period.

Market Segmentation:Segmentation 1: by Application Earth Observation Communication Navigation

Based on application, the space in-orbit refueling market is expected to be dominated by the communication segment owing to its technological and economic feasibility. Communication and Earth observation applications are expected to see the first initial missions for refueling.

Segmentation 2: by End-User Commercial Other End Users

Based on end-user, the space in-orbit refueling market is expected to be dominated by commercial end-users.Commercial end-users are expected to garner significant share and growth due to their priority requirement and economic feasibility.

Commercial satellite operators with large satellite constellations and heavy communication satellites are expected to adopt the technologies faster compared to any other segment.

Segmentation 3: by Region North America Europe Asia-Pacific

During the forecast period, North America is expected to dominate the space in-orbit refueling market (by region).The significant presence of key companies engaged in developing space in-orbit refueling services is a major factor responsible for the regions growth.

A higher number of collaborations between various service providers, satellite operators, and enabling technology providers is another factor driving the market growth. An increasing number of start-ups and emerging players and successful demonstrations and increasing investments by key players in the market are also contributing to the market growth.

Recent Developments in the Space In-Orbit Refueling Market

In January 2022, Astroscale Holdings Inc. and Orbit Fab, Inc signed a commercial agreement for refueling LEXI in the GEO orbit. LEXI is the first satellite that is designed to be refueled. As per the agreement, Orbit Fab, Inc will refuel Astroscales fleet of LEXI Servicers with up to 1000 kgs of Xenon Propellant. To develop technologies for cryogenic propellant storage and transfer, with these awards, NASA is investing in technologies for the storage and transfer of cryogenic propellants in space. Four awards worth more than $250 million went to companies working on cryogenic fluid management. To demonstrate refueling a GEO satellite, Northrop Grummans Mission Extension Vehicle-1 (MEV-1) docked with Intelsat 901 on 25th February 2020 and pushed the satellite back to its normal orbit. Northrop Grummans MEVs are expected to give more than 15 years of life extension to these satellites along with providing spacecraft inspections, inclination changes, and orbit repair. In April 2022, Washingtons Defense Innovation Unit (DIU) is planning to provide commercial refilling services in near the prime space real estate of Geosynchronous Orbit, commonly referred to as GEO. Its also planning on creating a bulk fuel depot in the orbits. DIU is looking for companies with the capability for bulk liquid and gas propellant storage (>5,000 kg) in orbit. Two of the propellants include hydrazine and liquid oxygen. In April 2022, Orbit Fab, Inc and Neutron Star Systems have announced a partnership for the co-development of sustainable propulsion capability and satellite refueling technologies. The agreement will help to increase the range of refuellable propellants by combining NSS propellant-agnostic electric propulsion technology with Orbit Fabs refueling interfaces and tankers.

Demand - Drivers and Limitations

Following are the drivers for the Space In-Orbit Refueling market: Increase in Demand for Sustainable and Reusable Space Systems Life Extension Services to Enable Other In-Orbit Services in Future

Following are the challenges for the Space In-Orbit Refueling market: High Operational Cost of Refueling Interface and Docking Regulatory Challenges Spacecraft Design Compatibility for Refueling Operations Storage and Transfer of Cryogenic Propellants in Space

Following are the opportunities for the Space In-Orbit Refueling market: Increase in Investments for Startups Rise in Demand for In-Space Services Advancement of New Space Technologies for Storage, Refueling, and Receiving Propellants

How can this report add value to an organization?

Product/Innovation Strategy: The product section will help the reader understand the different solutions for the space in-orbit refueling and services market, such as the type of capabilities and emerging technologies.It will also help readers understand the potential of the services at a global level and learn about their progress.

The players operating in these markets are developing innovative offerings and are deeply engaged in long-term agreements and contracts with commercial and government agencies. Moreover, the study also examines the investment scenario in the space in-orbit refueling and services market.

Growth/Marketing Strategy: The players operating in the space in-orbit refueling market are engaged in several strategies, including strategic partnerships, contracts, agreements, and business expansion. The marketing strategies will help the readers understand the revenue-generating strategies adopted by the in-orbit service providers operating in the space in-orbit refueling market.

For instance, Orbit Fab, Inc and the U.S. Air Force Research Laboratory have signed a technology-sharing agreement to share details regarding RAFTI. The company markets its products to all different layers of the military, intelligence, and commercial satellite community. The Air Force will help Orbit Fab review some of the technologies that aided in developing them. More specifically, they are going to advise on requirements and design elements, as well as provide testing and qualification access at several governmental facilities throughout the country.

In February 2022, Northrop Grumman-owned SpaceLogictics has signed a launch agreement with SpaceX and a contract with Optus for the sale of its Mission extension pod. Under the agreement, SpaceX will be responsible for providing launch services for the 2024 MRV and MEP launches.

Competitive Strategy: The study has analyzed and profiled the key service providers, start-ups, and emerging players in the space in-orbit refueling market.These companies capture the maximum share in the global space in-orbit refueling market.

Additionally, a detailed competitive benchmarking of the companies and organizations operating in the space in-orbit refueling market has been carried out, which will help the reader to understand the performance of the players, exhibiting a clear market landscape. In addition to this, comprehensive competitive strategies such as partnerships, agreements, and collaborations will aid the reader in understanding the potential revenue opportunities in the market.

Key Market Players and Competition Synopsis

The companies profiled in the study have been selected based on inputs gathered from primary experts and analysis of the companies product portfolios, key developments, and market penetration.

Space in-orbit refueling as a technology is still in the development and demonstration phase.However, there are several established players and startups that have entered the market and have made considerable progress.

Considering the present market scenario and future forecasts, the market is expected to grow at a CAGR of 103.85% by 2032.

Some prominent established names in this market are: Astroscale Holdings Inc. Altius Space Machines, Inc. D-Orbit SpA Lockheed Martin Corporation LMO Space Maxar Technologies Inc. Momentus Space Orbit Fab, Inc. Obruta Space Solutions Orbit Recycling SpaceX SpaceLogistics (a subsidiary of Northrop Grumman Corporation) Space Machines Company Starfish Space Inc. Tethers Unlimited, Inc.

Countries Covered North America U.S. Canada Europe Germany Russia France U.K. Rest-of-Europe Asia-Pacific India Japan Rest-of-Asia-PacificRead the full report: https://www.reportlinker.com/p06317753/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

__________________________

Originally posted here:
Space In-Orbit Refueling Market - A Global and Regional Analysis: Focus on Application, End User, Capability, and Country - Analysis and Forecast,...

Recommendation and review posted by Bethany Smith

Pune, Maharashtra, India, September 19 2022 (Wiredrelease) Prudour Pvt. Ltd :Global Stem Cell Banking Market: Introduction

Stem cells are capable of transforming into any kind of tissue or organ in the body. Stem cells are found in bone, bone marrow, fetal tissue, baby teeth, fat and human embryos. They can also be found in hair follicles, muscle and circulating blood. Cord blood is a great source of stem cell. Cord blood stem cells have several advantages. They are less likely to be rejected by the immune system during transfusions, and they can be more effective in transplant. Stem cell banking has seen an increase in demand due to numerous applications, including treatment for various diseases such as cancer. These stem cells are taken from the human body and stored for future usage.

The global stem cell banking market is projected to reach USD 9.42 billion by 2023 from USD 6.29 million in 2018, at a CAGR of 8.5% from 2018 to 2023.

Stem Cell Banking Market DynamicsThis section discusses market drivers, opportunities, limitations, and challenges. The following details are provided:

Drivers: Stem Cell Banking Requirements

The markets major drivers are the increase in the worldwide burden of major diseases and the increasing use of stem cell banking to cure severely damaged tissues. The markets growth is expected to be driven by the increased use of hematopoietic and brain stem cell transplantation procedures, as well as the rise in skin transplants and brain cells transplantations.

Surging Awareness

The market will benefit from awareness campaigns by both government and non-government agencies to promote stem cell therapy.

Opportunities: Growing Investments and Advancements

Market growth will be driven by the development and commercialization of new technologies that preserve, process, and store stem cells. Market growth opportunities will also be provided by increasing investments in stem-cell-based research.

Restraints/Challenges Global Stem Cell Banking Market: High-Cost

The high operating costs associated with stem cell transplantation are expected to slow down market growth.

In the 2022-2029 forecast period, stem cell banking will face challenges due to the stringent regulatory frameworks as well as socio-ethical concerns relating to embryonic stem cell.

Recent Developments

Life Cell International (India), has launched an improved and enhanced umbilical cord collection tool in 2017.

2017 saw Vita34 AG acquire Seracell Pharma AG (Germany), in order to consolidate its position within the German stem-cell banking market.

StemCyte India Therapeutics Pvt. Ltd. (India), which is a subsidiary of StemCyte US, received accreditation from The Foundation for the Accreditation of Cellular Therapy. It can provide stem cell banking services for private and public clients.

Cord Blood Registry, (US) signed an agreement with New York Stem Cell Foundation in 2015 to create induced pluripotent (SP) stem cells from umbilical chords.

Identify the key factors that will drive your companys growth. Request a brochure of this report here:https://market.us/report/stem-cell-banking-market/request-sample/

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Stem Cell Banking Market Competitive Landscape

CCBCCBRViaCordEsperiteVcanbioBoyalifeLifeCellCrioestaminalRMS RegrowCordlife GroupPBKM FamiCordcells4lifeBeikebiotechStemCyteCryo-cellCellsafe Biotech GroupPacifiCordAmericordKrioFamilycord

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Stem Cell Banking Market Segmentation

Based on the type, the Stem Cell Banking market is segmented into

Umbilical Cord Blood Stem CellEmbryonic Stem CellAdult Stem Cell

Based on the application, the Stem Cell Banking market is segmented into

Diseases TherapyHealthcare

Market Breakup by Region:

North America (United States, Canada)

Asia Pacific (China, Japan, India, South Korea, Australia, Indonesia, Others)

Europe (Germany, France, United Kingdom, Italy, Spain, Russia, Others)

Latin America (Brazil, Mexico, Others)

The Middle East and Africa

Market Report Coverageand Deliverables will help you to understand:

1. Company revenue shares | revenue (US$ Mn)

2. Upcoming Regional opportunities

3. Latest trends & Market dynamics

4. Competitive benchmarking

5. Key Financial Charts

Grab the full detailed report here:https://market.us/report/stem-cell-banking-market/

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Q1. What is the market size of Stem Cell Banking?

Q2. What are the elements of retail Stem Cell Banking?

Q3. What are the key decision drivers for service buyers?

Q4. How can we accelerate our bidding process?

Q5. What is the potential of the Stem Cell Banking Market?

Q6. Who are the prominent players in Stem Cell Banking Market?

Q7. What are the different types of Stem Cell Banking market?

Q8. What are the top strategies that companies adopt in Stem Cell Banking Market?

Q9. What is the future of Stem Cell Banking?

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Link:
Stem Cell Banking Market to Cross USD 9.42 Bn; Short-term Decline to Be Witnessed amidst COVID-19 Pa - PharmiWeb.com

Recommendation and review posted by Bethany Smith

MIRAMAR, FL, Sept. 19, 2022 (GLOBE NEWSWIRE) -- Stemtech Corporation (Stemtech) (OTCQB: STEK), an innovative nutraceutical company and a pioneer in the field of stem cell nutrition, today announced creation of new stem cell skincare products.

Stemtech Corporation President and Chief Operating Officer, John W. Meyer, said the introduction of the stem cell skincare line is very exciting for us to offer our Independent Business Partners (IBPs) and customers. The product will be introduced at the upcoming Cancun, Mexico Incentive Meeting in December. Meyer continues to say that Stemtechs belief in highly efficacious and quality products expands into a very important area for youthful and healthy skin care. The skincare, along with our stemceutical products of RCM - stemrelease3, StemFlo Advanced and MigraStem, is a winning combination for inner health and outer radiance - fantastic! We all want to feel better, look better. By using Stemtech products, you can!

Fortune Business Insights in August 2021 published that the global skincare market is projected to grow from $100.13 billion in 2021 to $145.82 billion in 2028 at a CAGR of 5.52% in forecast period, 2021-2028. Meyer continues, noting while it may seem that there are many companies already in this space, Stemtech feels confident with our new science being developed, we will have a significant impact on the skincare market using our stem cell scientific knowledge.

Charles S. Arnold, Stemtech Corporation Chairman and CEO stated that the introduction of skincare focuses new Stemtech stem cell technology on skincare for healthier skin, the largest organ of the body, which we recognize as a key to anti-aging. Our excitement at being able to launch new products, complete with samples, for a more youthful and healthy skin will catapult our Field to new growth and revenue opportunities. We know our IBPs will be exuberant with this great new Stemtech Skincare product line.

About Stemtech Corporation

Stemtech Corporation, a leading nutraceutical company with a direct sales distribution model, was founded on April 18, 2018, after acquiring the operations from its predecessor Stemtech International, Inc. which was founded in 2005. From 2010 through 2015, Stemtech International, Inc., was recognized four separate times on the Inc. 5000 Fastest-Growing Companies list. In 2018, the Company underwent an extensive executive reorganization, and continued operations under new leadership. Stemtech specializes in creating products and formulas that are patent protected in the U.S. and in select international markets. The Companys patented formulas help the release, circulation and migration of the bodys adult stem cells from its bone marrow. The Company markets its products under the following brands: RCM System, stemrelease3, Stemflo MigraStem, OraStem (Oral Health Care), and D-Fuze (EMF blocker). Its nutraceutical products are all-natural, plant-based and manufactured under cGMP (Current Good Manufacturing Practices) under the auspices of the Dietary Supplement Health and Education Act (DSHEA). For more information, please visit http://www.stemtech.com.

Forward-Looking Statements

This announcement contains forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements identified by words such as "believes," "expects," "anticipates," "estimates," "intends," "plans," "targets," "projects" and similar expressions. The statements in this release are based upon the current beliefs and expectations of our company's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements. Numerous factors could cause or contribute to such differences, including, but not limited to, results of clinical trials and/or other studies, the challenges inherent in new product development initiatives, the effect of any competitive products, our ability to license and protect our intellectual property, our ability to raise additional capital in the future that is necessary to maintain our business, changes in government policy and/or regulation, potential litigation by or against us, any governmental review of our products or practices, as well as other risks discussed from time to time in our filings with the Securities and Exchange Commission, including, without limitation, our latest 10-Q Report filed onAugust 23, 2022. We undertake no duty to update any forward-looking statement, or any information contained in this press release or in other public disclosures at any time. Finally, the investing public is reminded that the only announcements or information about Stemtech Corporation which are condoned by the Company must emanate from the Company itself and bear our name as its Source.

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Investor Relations: Investor Relations: 954-715-6000 ext 1040invrel@stemtech.com

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STEMTECH CORPORATION ANNOUNCES THE INTRODUCTION OF A NEW - GlobeNewswire

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Five people with the autoimmune condition lupus are now in remission after receiving a version of CAR-T therapy, which was originally developed for cancer

By Clare Wilson

Illustration of a CAR-T cell

CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY

A high-tech cell therapy used to treat cancer has been repurposed as a treatment for lupus, an autoimmune condition that can cause joint, kidney and heart damage.

CAR T-cell therapy has put all five people with lupus treated so far into remission. The participants have been followed up for an average of 8 months, with the first person treated 17 months ago. Thats kind of unheard of, says Chris Wincup at Kings College London, who wasnt involved in the study. This is incredibly exciting.

But it is too soon to know how long the remissions will last, says Georg Schett at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

CAR T-cells were developed to treat blood cancers that arise when B cells, a type of immune cell that normally makes antibodies, start multiplying out of control.

The approach requires taking a sample of immune cells from a persons blood, genetically altering them in the lab so they attack B cells and then infusing them back into the individuals blood. It seems to put 4 out of 10 people with these kinds of cancers into remission.

Lupus, also called systemic lupus erythematosus, is caused by the immune system mistakenly reacting against peoples own DNA. This is driven by B cells making antibodies against DNA released from dying cells.

It is currently treated with medicines that suppress the immune system or, in more severe cases, with drugs that kill B cells. But the treatments cant kill all the B cells, and if the disease flares up badly, some people develop kidney failure and inflammation of their heart and brain.

Schett and his team wondered whether using CAR T-cells to hunt down all the B cells would be more effective. Within three months of receiving the treatment, all five participants were in remission, without needing to take any other medicines to control their symptoms.

The CAR T-cells were barely detectable after one month, and after three and a half months, the volunteers B cells started to return, having been produced by stem cells in bone marrow. These new B cells didnt react against the DNA.

We dont know what normally causes B cells to start reacting against DNA in people with lupus, so it is possible that some kind of trigger may start the process happening again, says Wincup.

The achievement means CAR T-cells may also be useful against other autoimmune diseases that are driven by antibodies, such as multiple sclerosis (MS), in which the immune system attacks nerves, says Schett.

Another radical treatment for MS involves rebooting the immune system by destroying it with chemotherapy. By comparison, CAR T-cells would be less invasive and more tolerable, he says.

But it is too soon to know how effective CAR T-cells will be for autoimmune conditions, says Wincup. This is a small number of patients, so we dont know if this is going to be the result for everyone.

When used in cancer, CAR T-cells are expensive to create for each person, so they may only be used for autoimmune conditions in people with severe disease when no other treatments are available, he says.

Journal reference: Nature Medicine , DOI: 10.1038/s41591-022-02017-5

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Radical lupus treatment uses CAR T-cell therapy developed for cancer - New Scientist

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Esteemed award is an international forum celebrating noteworthy achievements in equine research and individuals who have significantly impacted equine health

The University of Kentucky (UK) Gluck Equine Research Center unveiled the 2022 inductees to the Equine Research Hall of Fame. The winners include Lisa Fortier, DVM, PhD, DACVS; Katrin Hinrichs, DVM, PhD; Jennifer Anne Mumford, DVM; and Stephen M. Reed, DVM.

The scientists were nominated by their fellow peers and past awardees. Nominees may be living or deceased, active in or retired from the field of equine research.

In research, we always stand on the shoulders of those who go before us with great discoveries. This years recipients have made substantial contributions that will ensure an excellent future for equine research, expressed Nancy Cox, UK vice president for land-grant engagement and College of Agriculture, Food and Environment dean, in a university release.1

The success of Kentuckys horse industry is inseparable from the decades of hard work by outstanding equine researchers, added Stuart Brown, chair of the Gluck Equine Research Foundation. Though impossible to measure, it is a unique privilege to recognize the impact made by these four scientists in advancing the health and wellbeing of the horse and, on behalf of the entire equine community, show our appreciation.

Below are the details of each awardee1:

Throughout the past 30 years, Fortier has been renowned for her substantial contributions in equine joint disease, cartilage biology, and regenerative medicine. Her research focuses on early diagnosis and treatment of equine orthopedic injuries to prevent permanent damage to joints and tendons. She is most well-known for her work in regenerative medicine, spearheading the use of biologics such as platelet rich plasma, bone marrow concentrate, and stem cells for use in horses and humans. Additionally, Fortiers lab has been key in strides associated with cartilage damage diagnosis and clinical orthopedic work.

Fortier achieved her bachelors degree and doctor of veterinary medicine degree from Colorado State University. She finished her residency at Cornell, where she also earned a PhD and was a postdoctoral fellow in pharmacology. Currently, she serves as the James Law Professor of Surgery at Cornells College of Veterinary Medicine. She is the editor-in-chief of the Journal of the American Veterinary Medical Association and serves on the Horseracing Integrity and Safety Authority Racetrack Safety Standing Committee.

Hinrichs dedicates her career to research mainly in equine reproductive physiology and assisted reproduction techniques. Her focus has consisted of equine endocrinology, oocyte maturation, fertilization, sperm capacitation, and their application to assisted reproduction techniques.

Her 40 years of research have resulted in various notable basic and applied research accomplishments. The applied achievements include generating the first cloned horse in North America and creating the medical standard for effective intracytoplasmic sperm injection and in vitro culture for equine embryo production. She has mentored over 85 veterinary students, residents, graduate students, and postdoctoral fellows in basic and applied veterinary research. Her laboratories have hosted about 50 visiting scholars worldwide.

Hinrichs achieved her bachelors degree and doctor of veterinary medicine degree from the University of California, Davis. She finished residency training in large animal reproduction at the University of Pennsylvanias New Bolton Center and received a PhD at the University of Pennsylvania.

Mumford is a posthumous inductee who received international respect as among the most prominent researchers of equine infectious diseases, specifically equine viral diseases. Her career at the Animal Health Trust, Newmarket, United Kingdom, began when she was deemed the first head of the newly established equine virology unit. Her work focused on the leading causes of acute infectious respiratory disease in the horse, mainly equine herpesvirus and equine influenza virus, and to a lesser extent,Streptococcus equi.

Mumford impacted several of these realms, including developing enhanced vaccines, diagnostics, and international surveillance. Additionally, she helped create research groups in the related fields of equine genetics and immunology.

Throughout Mumfords over 30 year-career, she helped the Animal Health Trust be recognized as one of the worlds leading centers for the study of the biology, epidemiology, immunology and pathology of diseases.

Reeds nominators deemed his as the last word in equine neurology. He is known as among the most prominent equine neurologists worldwide. His list of 180 peer-reviewed publications feature important contributions to equine medicine, neurology, physiology and pathophysiology. He has shared in his accomplishments as a mentor and role-model for hundreds of aspiring equine practitioners.

Reed received his bachelors degree and doctor of veterinary medicine degree from The Ohio State University. He finished his internship and residency training in large animal medicine at Michigan State University.

The UK Gluck Equine Research Foundation will induct the 4 winners into the UK Equine Research Hall of Fame October 26, 2022 at Kroger Field in Lexington, Kentucky.

Reference

Wiemers H. UK Equine Research Hall of Fame inductees announced. UK College of Agriculture, Food and Environment. News release. September 13, 2022. Accessed September 20, 2022. https://news.ca.uky.edu/article/uk-equine-research-hall-fame-inductees-announced-1

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University of Kentucky Equine Research Hall of Fame announces awardees - DVM 360

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