Archive for the ‘Crispr’ Category

Doctors at the University of Pennsylvania Abramson Cancer Centre say it could hail a new era of potential treatments

A DNA editing tool used to snip defective genes in unborn children is being tested in the United States to fight cancer.

For the first time outside of China, tests on three patients with advanced cancer were conducted to see how effective DNA-snipping tool Crispr is at fighting the disease.

Doctors at the University of Pennsylvania Abramson Cancer Centre used the technology on patients in their 60s whose cancer had progressed despite undergoing regular treatments such as chemotherapy, radiation and surgery.

Its the most complicated genetic, cellular engineering thats been attempted so far, said study leader Dr Edward Stadtmauer, the centres section chief of hematologic malignancies.

This is proof that we can safely do gene editing of these cells.

The technique extracts immune cells from the patients blood and genetically alters them to recognise and fight cancer cells.

Experts said early tests proved to be safe, and that a breakthrough could hail a new era of potential cancer treatments.

Two of the patients had blood cancer and the other had a rarer form of sarcoma, cancer of the bone or soft tissue.

Although yet to be published in a peer-reviewed medical journal, the findings will be presented at the American Society of Hematology in December.

Researchers said the exercise at this stage was focused on whether the technology is safe and feasible, rather than improving survival rates. It is too early to say whether the treatment will improve survival rates.

The use of Crispr technology in China to edit the genes of couples experiencing fertility problems has been controversial.

The editing tool alters a defective gene in IVF embryos to eliminate life-limiting or chronic illnesses such as sickle cell disease, which starves the body of oxygen.

Some doctors have criticised the early use of the molecular scissors in fertility clinics as the long term effects are not yet known, with potential damage caused to other genes during the treatment.

Updated: November 17, 2019 11:28 AM

Originally posted here:
US cancer scientists on the verge of gene editing breakthrough to treat cancer - The National

CRISPR, the revolutionary ability to snip out and alter genes with scissor-like precision, has exploded in popularity over the last few years and is generally seen as the standalone wizard of modern gene-editing. However, its not a perfect system, sometimes cutting at the wrong place, not working as intended and leaving scientists scratching their heads. Well, now theres a new, more exacting upgrade to CRISPR called Prime, with the ability to, in theory, snip out more than 90% of all genetic diseases.

Just what is this new method and how does it work? We turned to IEEE fellow, biomedical researcher and dean of graduate education at Tuft Universitys school of engineering Karen Panetta for an explanation.

CRISPR is a powerful genome editor. It utilizes an enzyme called Cas9 that uses an RNA molecule as a guide to navigate to its target DNA. It then edits or modifies the DNA, which can deactivate genes or insert a desired sequence to achieve a behavior. Currently, we are most familiar with the application of genetically modified crops that are resistant to disease.

However, its most promising application is to genetically modify cells to overcome genetic defects or its potential to conquer diseases like cancer.

Some applications of genome editing technology include:

Of course, as with every technology, CRISPR isnt perfect. It works by cutting the double-stranded DNA at precise locations in the genome. When the cells natural repair process takes over, it can cause damage or, in the case where the modified DNA is inserted at the cut site, it can create unwanted off-target mutations.

Some genetic disorders are known to mutate specific DNA bases, so having the ability to edit these bases would be enormously beneficial in terms of overcoming many genetic disorders. However, CRISPR is not well suited for intentionally introducing specific DNA bases, the As, Cs, Ts and Gs that make up the double helix.

Prime editing was intended to overcome this disadvantage, as well as other limitations of CRISPR.

Prime editing can do multi-letter base-editing, which could tackle fatal genetic disorders such as Tay-Sachs, which is caused by a mutation of four DNA letters.

Its also more precise. I view this as analogous to the precision lasers brought to surgery versus using a hand-held scalpel. It minimized damage, so the healing process was more efficient.

Prime editing can insert, modify or delete individual DNA letters; it also can insert a sequence of multiple letters into a genome with minimal damage to DNA strands.

Imagine being able to prevent cancer and/or hereditary diseases, like breast cancer, from ever occurring by editing out the genes that are makers for cancer. Cancer treatments are usually long, debilitating processes that physically and emotionally drain patients. It also devastates patients loved ones who must endure watching helpless on the sidelines as the patient battles to survive.

Editing out genetic disorders and/or hereditary diseases to prevent them from ever coming to fruition could also have an enormous impact on reducing the costs of healthcare, effectively helping redefine methods of medical treatment.

It could change lives so that long-term disability care for diseases like Alzheimers and special needs education costs could be significantly reduced or never needed.

How did the scientific community get to this point where did CRISPR/prime editing come from?

Scientists recognized CRISPRs ability to prevent bacteria from infecting more cells and the natural repair mechanism that it initiates after damage occurs, thus having the capacity to halt bacterial infections via genome editing. Essentially, it showed adaptive immunity capabilities.

Its already out there! It has been used for treating sickle-cell anemia and in human embryos to prevent HIV infections from being transmitted to offspring of HIV parents.

IEEE engineers, like myself, are always seeking to take the fundamental science and expand it beyond the petri dish to benefit humanity.

In the short term, I think that Prime editing will help generate the type of fetal like cells that are needed to help patients recover and heal as well as developing new vaccines against deadly diseases. It will also allow researchers new, lower cost alternatives and access to Alzheimers like cells without obtaining them post-mortem.

Also, AI and deep learning is modeled after human neural networks, so the process of genome editing could potentially help inform and influence new computer algorithms for self-diagnosis and repair, which will become an important aspect of future autonomous systems.

Continued here:
Youve heard of CRISPR, now meet its newer, savvier cousin CRISPR Prime - TechCrunch

PHOTO: BARBARA RIES FOR UCSF

There are key moments in the history of every disruptive technology that can make or break its public perception and acceptance. For CRISPR-based genome editing, such a moment occurred 1 year agoan unsettling push into an era that will test how society decides to use this revolutionary technology.

In November 2018, at the Second International Summit on Human Genome Editing in Hong Kong, scientist He Jiankui announced that he had broken the basic medical mantra of do no harm by using CRISPR-Cas9 to edit the genomes of two human embryos in the hope of protecting the twin girls from HIV. His risky and medically unnecessary work stunned the world and defied prior calls by my colleagues and me, and by the U.S. National Academies of Sciences and of Medicine, for an effective moratorium on human germline editing. It was a shocking reminder of the scientific and ethical challenges raised by this powerful technology. Once the details of He's work were revealed, it became clear that although human embryo editing is relatively easy to achieve, it is difficult to do well and with responsibility for lifelong health outcomes.

It is encouraging that scientists around the globe responded by opening a deeper public conversation about how to establish stronger safeguards and build a viable path toward transparency and responsible use of CRISPR technology. In the year since He's announcement, some scientists have called for a global but temporary moratorium on heritable human genome editing. However, I believe that moratoria are no longer strong enough countermeasures and instead, stakeholders must engage in thoughtfully crafting regulations of the technology without stifling it. In this vein, the World Health Organization (WHO) is pushing government regulators to engage, lead, and act. In July, WHO issued a statement requesting that regulatory agencies in all countries disallow any human germline editing experiments in the clinic and in August, announced the first steps in establishing a registry for future such studies. These directives from a global health authority now make it difficult for anyone to claim that they did not know or were somehow operating within published guidelines. On the heels of WHO, an International Commission on the Clinical Use of Human Germline Genome Editing convened its first meeting to identify the scientific, medical, and ethical requirements to consider when assessing potential clinical applications of human germline genome editing. The U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the Royal Society of the United Kingdom lead this commission, with the participation of science and medical academies from around the world. Already this week, the commission held a follow-up meeting, reflecting the urgent nature of their mission.

Where is CRISPR technology headed? Since 2012, it has transformed basic research, drug development, diagnostics, agriculture, and synthetic biology. Future CRISPR-based discoveries will depend on increased knowledge of genomes and safe and effective methods of CRISPR delivery into cells. There needs to be more discussion about prioritizing where the technology will have the most impact as well as equitable, affordable access to its products. As for medical breakthroughs, clinical trials using CRISPR are already underway for patients with cancer, sickle cell disease, and eye diseases. These and many other future uses of genome editing will involve somatic changes in individuals, not heritable changes that are transmissible. But the rapidly advancing genome editing toolbox will soon make it possible to introduce virtually any change to any genome with precision, and the temptation to tinker with the human germ line is not going away.

The CRISPR babies saga should motivate active discussion and debate about human germline editing. With a new such study under consideration in Russia, appropriate regulation is urgently needed. Consequences for defying established restrictions should include, at a minimum, loss of funding and publication privileges. Ensuring responsible use of genome editing will enable CRISPR technology to improve the well-being of millions of people and fulfill its revolutionary potential.

* J.D. is a cofounder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, and Mammoth Biosciences; scientific advisory board member of Caribou Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Synthego, and Inari; and director at Johnson & Johnson. Her lab has research projects sponsored by Biogen and Pfizer.

The rest is here:
CRISPR's unwanted anniversary - Science Magazine

Susanna M. Hamilton/Broad Communications

Susanna M. Hamilton/Broad Communications

It's not easy to treat viral infections. Just ask anyone with a bad cold or a case of the flu.

But scientists in Massachusetts think they may have a new way to stop viruses from making people sick by using what amounts to a pair of molecular scissors, known as CRISPR.

It's a gene editing tool based on a molecule that occurs naturally in microorganisms.

CRISPR comes in many "flavors" that perform a variety of functions inside cells. The Cas9 flavor has been widely used as a tool for editing DNA inside cells. It's already shown promise for medical therapies such as treating sickle cell disease.

What's different is that the antiviral approach researchers at the Broad Institute in Cambridge are using involves a form of CRISPR called Cas13 that targets specific regions of RNA, not DNA.

RNA is a chemical cousin of DNA. Many viruses, including flu and Zika, package their genetic instructions in RNA instead of DNA.

When a virus infects a cell in our bodies, it hijacks the cell's molecular machinery to make copies of itself. Those new viruses can go on to spread the infection through your body.

So for therapy, "we need to be able to cut the virus at a fast enough rate to slow down replication or to stop replication from happening," says Cameron Myhrvold, a postdoc at the Broad Institute.

Finding the right target is key. There's a lot of RNA inside cells that is necessary for the cell to survive, so it's important to find an RNA target that's unique to the virus you're trying to control.

Myhrvold says RNA viruses are particularly difficult to control because they are a bit like shape-shifters: They tend to change their genetic sequences when you try to pin them down. That's one of the reasons people need a new flu vaccine each year.

Understanding how the virus changes in response to Cas13 treatment should be informative.

"That could potentially teach us about what parts of the virus are particularly important for its function," says Catherine Freije, a doctoral student at the Broad Institute. And that in turn will show the best places to target the virus in order to disable it.

So far, Freije and Myhrvold say they've only shown their antiviral treatment works in cells.

But Pardis Sabeti, head of the lab they work in, is bullish about using the CRISPR Cas13 system to treat viral infections in people.

"There's still a bunch of things we want to work out, but we feel pretty confident that this will work as a therapy if it can be delivered in the right way," Sabeti says.

By delivering, she means getting the CRISPR Cas13 tool into the right cells inside an infected patient.

Since CRSIPR Cas13 specifically targets RNA, it will only be useful for illnesses caused by RNA.

Janice Chen says researchers are now finding a variety of CRISPRs with different properties. Chen is chief research officer at Mammoth Biosciences, a company that hopes to capitalize on CRISPR technology.

"Having a broader CRISPR toolbox is really important to figure out what is the specific need for any given application," Chen says.

Progress in building that toolbox has proceeded quite quickly. After all, it's only been six years since scientists first became aware of how powerful a tool CRISPR could be.

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CRISPR Could Stop Replication Of Viruses That Cause Illness, Researchers Say : Shots - Health News - NPR

These three health and technology stocks are on the move and pointing higher.

Advanced Micro Devices Inc. AMD, +0.55% jumped 81 cents to $37.52 on 67 million shares traded Wednesday. On Tuesday, the chip maker announced Tencent TCEHY, +0.20% will use its latest server processors. The stock has been in a steep rising channel since its recent low below $28 in early October. Next target is the rising channel top near $40.

Amarin Corp. PLC AMRN, +11.77% followed through on Wednesday, up 55 cents to $21.49 after popping 23% on Tuesday. An FDA advisory committee is scheduled to meet today to help decide the fate of the companys fish-derived cardiovascular drug. While trading has been halted this morning in advance of the meeting, the chart points to a test of the July high in the $23.50-$24.00 zone next.

Crispr Therapeutics AG CRSP, +3.29% rose $1.42 to $55 on 1 million shares Wednesday. The move, on no news from the company, continued the gene-editings stocks month-long rally from around $36. It also followed through on Tuesdays breakout of a mini-wedge. Watch for a move to $58 next.

See Harrys video-chart analysis on these stocks.

The writer has no holdings in any securities mentioned.

Harry Boxer is founder of TheTechTrader.com, a live trading room featuring his stock picks, technical market analysis and live chart presentations.

Read more here:
AMD, Amarin and Crispr are three stocks to watch for potentially higher prices - MarketWatch

In Europe, we dont do things the way the Americans do

Oral proceedings in the opposition against UC Berkeleys (UCs) main European patent EP2800811 are scheduled for all of three (!) days in February of 2020 at the European Patent Office (EPO). The opposition divisions (ODs) preliminary and non-binding opinion, provided on the 30th of August 2019 in preparation for the hearing, is favorable to the patentee. In its opinion, the OD sides with UC Berkeley and dismisses the main arguments of the seven opponents. Arguments relating to minor issues of added subject matter have been accepted by the OD, however UC is likely to be able to overcome these. Thus, there is a chance that UC Berkeley will keep their strong hold on rights to general platform Crispr technology in Europe.

UC Berkeleys patent claims priority from four provisional US applications. The question of whether the priority from the first provisional application P1 is valid or not lies at heart of the case.

According to European practice, G2/98, the requirements of claiming priority of the same invention in the meaning of Art 87(1) EPC mean that priority can only be acknowledged if the skilled person can derive the subject matter directly and unambiquously, using common general knowledge (CGK), from the previous application as a whole. In addition, the priority document must provide an enabling disclosure, in other words, all essential elements needed to carry out the invention must be disclosed in the priority document.

The opponents argue that P1 fails to provide an enabling disclosure, as it does not disclose or exemplify elements which are essential for the workability of the Crispr-Cas9 system in eukaryotic cells. At the heart of this issue is the protospacer adjacent motif (PAM), a 2-6 base pair DNA sequence which immediately follows the target DNA sequence and is an essential targeting component. The opponents argue that without knowledge of a PAM sequence, a person skilled in the art was not in a position to design an appropriate guide RNA and would therefore not have been able to achieve cleavage of target DNA (as the Cas9 endonuclease will not recognize target DNA without the PAM).

UC replies that the requirement of a PAM to be located downstream of the target DNA sequence was CGK at the date of filing of P1 and therefore the omission of any reference to PAM is of no detriment to the disclosure of P1. UC states that the skilled persons understanding of this was confirmed by the sequences disclosed in P1, wherein the amino acid sequences corresponding to PAMs are present immediately downstream of the target DNA.

If the priority claim from P1 is found to be invalid, the effective date of the patent at hand would be after UCs scientific paper on Crispr-Cas9 was published in Science. This would be detrimental to the patentability of at least some of the claims.

However, UC was successful during the examination before the EPO, as well as in the corresponding UK cases, in arguing that PAM was part of CGK. By accepting in their preliminary opinion that PAM was part of the CGK at the time of filing of P1, the OD has provisionally concluded that the disclosure of P1 is enabling over the whole claim scope, encompassing eukaryotic applications.

Concerning what actually was CGK at the time, UC argues that CGK was represented by review and research articles in the fast-evolving new technology area. UC holds that such articles confirm that the requirement for PAM in the target DNA was CGK. Although full of references to CGK and the skilled person, the preliminary opinion does not dwell on the identity of the skilled person. Establishing the identity of the skilled person is likely to be important during the oral proceedings. Not limited to PAM, the opponents argue that several lines of technical information are missing in P1 and that a skilled person operating within the limits of what is explicitly defined in P1 would be confronted with an inacceptable degree of failure.

The OD has also come to the preliminary view that the claims are novel and exhibit inventive step. The inventive step analysis is based on the problem-solution approach starting from a prior art document from the TALEN field of gene editing, and not from the Crispr-field, based on the purpose of the UC invention. The technical problem solved by the invention is considered to be to provide a more versatile gene editing system. The OD adds that the Examples in the patent show that UCs invention achieves this, or at least renders the achievement credible, also for eukaryotic cells.

UCs position is that P1 not only claimed a new class of endonucleases, but also provided ample guidance on how to use the endonuclease complex for example in eukaryotic systems as, amongst other things, P1 disclosed expression systems including vectors suitable for eukaryotic expression. They point to the fact that several groups in the scientific community quickly, upon publication of the Science paper, confirmed that the Crisp-Cas9 system could be used for gene editing in eukaryotic cells.

Interestingly, the OD takes no notice of UC inventors Doudnas and Charpentiers public statements, made upon publishing of the Science paper, about unpredictability and technical challenges of adapting the Crispr-Cas9 system to eukaryotic gene editing. In fact, the OD underlines the difference between the question of obviousness in the US interference proceedings by exclaiming under US law! in the opinion and the question of plausibility in the present case. Although plausibility is not a term used in the European Patent Convention, it is increasingly more discussed. According to case law, however, the question of plausibility only comes into play if experimental data is lacking. The OD states in its opinion that this does not apply to present case, because the disclosure does contain experimental data.

Nevertheless, plausibility, as well as the identity of the skilled person, are likely to be discussed during the oral proceedings. Is the skilled person going to be someone from the TALEN field? If so, would they be expected to know all the details and nuances of the Crispr-Cas9 field or not? The identity of the skilled person may have implications on several aspects of the case.

For now, it appears that the differences between the European and US patent landscape in the Crispr-Cas9 field may remain, at least as indicated by the non-binding and preliminary opinion of the OD.

See the rest here:
The Crispr-Cas9 patent tussle continues: The case of UC Berkeley at the EPO - Lexology

Over the last few years, thousands of studies have employed CRISPR/Cas systems to edit, or transcriptionally regulate, individual genetic targets. But a new study has taken CRISPR to soaring heights.

CRISPR/Cas is remarkably simple in principle: a protein, usually Cas9, can bind to an RNA molecule, such as a single guide RNA (sgRNA), which has a sequence complementary to a target site in the genome. When the Cas9:sgRNA complex binds to its target site, it cleaves the target DNA. By mutating specific amino acids in Cas9, DNA cleavage activity is abolished, thus converting it into a transcriptional repressor (called dCas9).

Though many research groups have explored methods to increase the number of sgRNAs that can be expressed at once in vivo, it has been a difficult challenge, in part, because sgRNAs have very repetitive elements. One part of the sgRNA, called the handle, is a 42-nucleotide strand of RNA that physically associates with Cas9. Unfortunately, most DNA synthesis manufacturers are unable to synthesize these repetitive elements, thus limiting the number of sgRNAs that can be assembled and expressed in living organisms.

In a new study, published in Nature Biotechnology, researchers from Penn State University have devised a method that enables 22 distinct sgRNAs to be expressed at once in bacterial cells. The solution? Design and characterize hundreds of non-repetitive genetic parts, including new sgRNA handles, that maintain their function but can actually be synthesized by DNA manufacturers.

I sat down with Alex Reis and Sean Halper (joint first authors) and Howard Salis (corresponding author and Associate Professor at Penn State University) to learn more about multiplexed CRISPR, how nonrepetitive parts are designed, and their plans for the future.

This interview with Alex Reis, Sean Halper and Professor Howard Salis on Simultaneous repression of multiple bacterial genes using nonrepetitive extra-long sgRNA arrays, published in Nature Biotechnology, has been edited for clarity. Words in parentheses are my own.

***

Niko McCarty: Can you tell me a bit about the inspiration behind this study? What was the impetus that made you look at the CRISPR multiplexing field and say, I bet we can improve the number of sgRNAs expressed at once in living cells?

Alex Reis: Well, five years ago, Sean Halper (co-first author) and I took a graduate level course with Professor Howard Salis, and we were exploring different ideas for scalable genetic circuit design. We kept going back to CRISPR because it is a scalable system; all you need to do to build complex CRISPR-based genetic circuits is express one protein regulator (Cas9), and a whole bunch of single-guide RNA regulators (sgRNAs). That was a very powerful idea to us, and we really wanted to scale that up. So this project was motivated from an application side, the desire to build larger genetic circuits.

Professor Howard Salis: When looking at this long DNA sequence or genetic circuit that we had designed for this class project, we basically saw that there were quite a few long regions of repetitive DNA. And if you were to copy-paste that sequence into an order form for any gene synthesis provider, it would immediately tell you, We cant make this. Its too long, too repetitive. So we knew that this was going to be a challenge for the CRISPR field as groups try to multiplex sgRNAs. If you redesign the whole system so that there is no more repetitive DNA, you would be able to build it easier, assemble it faster, and you would be able to express a lot more CRISPR regulators simultaneously.

Niko: Can you walk me through the key advancements from the paper, especially the things that you set out to do and what you accomplished?

Alex: After we identified that repetitive DNA was going to be a key bottleneck in cloning sgRNA arrays, we decided that the first step would be to identify and characterize non-repetitive parts for both genetic expression and the sgRNA handles themselves. The first thing we did was to design and characterize non-repetitive promoters and non-repetitive terminators. But a key challenge that that we faced was to identify non-repetitive handle sequence for sgRNAs. What sequences will enable handle sequence variants to still bind to the Cas9 or dCas9 protein?

To design these non-repetitive sgRNA handles, we carried out multiple rounds of a design, build, and test cycles and imposed specific constraints. In the first design round, the constraint was purely structural we told our algorithm that the sgRNA had to fold into a structure that could be recognized by the Cas9 structure. After that round, we applied a machine learning technique called linear discriminant analysis to identify which mutations would cause handle failure. With that, we identified two nucleotides in the sgRNA handle, G43 and G52 that, when mutated, would abolish handle function. After iterating through these processes a few times, we ultimately characterized 28 highly functional, non-repetitive handle variants. And these handles work equally well for Cas9 and dCas9.

Grace Vezeau, another author on the paper, ran a bunch of cleavage assays to verify, measure and quantify how well these different non-repetitive sgRNA handles were able to load up into Cas9 and cleave DNA.

Niko: After you verified these non-repetitive sgRNA handles, you then used them for three different engineering applications. Can you walk me through those?

Sean Halper: We built three different ELSAs (extra long sgRNA arrays), the longest of which contained 22 distinct sgRNAs. We wanted to come up with some applications that would show the power of scaling up the number of sgRNAs using nonrepetitive handles in E. coli. Our first proof-of-concept was to aerobically produce succinate using a knockdown of six different genes. At first, when we targeted these six genes, it didnt work. We troubleshooted the problem, and found that we had to increase the expression of dCas9, after which we saw a 1000-fold knockdown on some of the genes that we were targeting. This incidentally also showed that, once you start expressing many sgRNAs at once, you need to have enough Cas9 or dCas9 to handle that many simultaneous RNA regulators.

In a second example, we used an ELSA to target different amino acid biosynthesis pathways. We really wanted to see if we could use CRISPRi knockdowns to impose auxotrophy-like behavior. For the third example, we knocked down different stress response genes to explore how a broad spectrum perturbation would affect the behavior and response of E. coli.

Howard: Part of this effort was also to develop algorithms that allow us to design DNA sequences that can be readily synthesized by commercial service providers. Some of these ELSAs have over 20 promoters, 20 terminators, and so forth. Terminators can form hairpins and may contain palindromic sequences, however, so if you ask a gene synthesis provider to synthesize any old DNA with lots and lots of hairpins, theyre going to balk at you. But if you design the system correctly, if you draw from a large enough pool or toolbox of genetic parts, and you arrange those genetic parts just right, you can meet your target metrics for what can be synthesized. As long as your DNA sequence is within those target metrics, then these companies can actually deliver the DNA fragments to you. By the end of this project, we were able to synthesize 33 DNA fragments up to 3 kilobases each, all containing ELSAs, with about a 90% success rate and turnaround time, which is about five days.

Niko: Do you have any plans for designing non-repetitive ribozymes or cleavage sites, which may enable you to express many sgRNAs from a single promoter?

Howard: Let me just start off by saying that we started this project four or five years ago, and we have made some important advancements since then. Another graduate student in our group, Ayaan Hossain, developed an algorithm called the Non-Repetitive Parts Calculator, which formalizes how you can go about designing very large toolboxes of non-repetitive genetic parts. With this algorithm, weve been able to design, construct and characterize huge toolboxes of non-repetitive parts, including 4300 non-repetitive E. coli promoters, 1917 non-repetitive yeast promoters, at least 600 non-repetitive ribozymes with near wildtype cleavage activities, and about 2000 non-repetitive Cas9 handles.

So, is it possible to design many more non repetitive parts? It is absolutely possible. We know that for sure. Theoretically, there are about 100,000 non-repetitive sgRNA handles out there for Cas9. We clearly havent characterized 100,000 yet, weve only characterized 2000, but that kind of gives you an order of magnitude for the possibilities. Now, it should be possible to arrange all these genetic parts in an array and build ELSAs that are about 500,000 bases long, which is smaller than many yeast chromosomes that labs have already built. So its possible to build these very long sgRNA arrays, and there are many applications for them across industrial metabolic engineering and in the biomedical space.

Niko: And what about the different authors on the paper? Were there specific skillsets brought by individuals?

Alex: Sean, myself and Phillip Clauer, a former undergraduate, did the bulk of the cloning and characterization of the parts, but most of the lab pitched in and helped out. Daniel Cetnar helped with RNA level characterization, including a lot of the early RT-qPCR on the CRISPRi knockdowns.

Sean: Ayaan Hossain was really helpful in terms of helping us expand our non-repetitive part libraries for the promoters and terminators especially, as well as helping with some of the machine learning analysis. But it was definitely a collaborative effort over the last five years.

Niko: What are your plans for after graduation?

Sean: I actually defended my PhD just a couple of weeks ago. Im part of the SMART Scholarship for Service program, which is a fellowship with the Department of Defense. Once I wrap up here, I plan on beginning work soon with my sponsoring facility, the Army Research Lab in Adelphi, Maryland.

Alex: Im wrapping up a project or two and then will hopefully graduate and move on to the next thing. I love synthetic biology, so I am looking at postdocs along those lines. Im also thinking about some entrepreneurial aspects that I could pursue.

Niko: This study is so appealing to me, in part, because of its collaborative nature. It seems like most people in the group helped out can you tell me a bit about that?

Howard: Well, we have a very relaxed environment. While some people in the synthetic biology field have groups with 30-40 people, our group has less than 10. This means that everyone knows everyone else, and we all help each other. I intentionally set up my lab so that new people come in, and they receive training not just from myself, but from other graduate students and postdocs. Because of this, many students feel the obligation to pay it forward and help out other people. If youre really good at something, and you can carry out some set of experiments quickly, then you should help out your colleagues in the lab. In our group, a lot of sharing goes on, and thats what makes work like this possible.

***

Biographies:

Howard Salis is an Associate Professor of Biological and Chemical Engineering and Synthetic Biology at Penn State University. Research in the Salis laboratory focuses on the development of rational design methods for engineering synthetic biological systems metabolic pathways, genetic circuits, and genomes.

Sean Halper is a graduate student at Penn State University, and co-first author on this study. He recently defended his PhD in Chemical Engineering.

Alex Reis is a graduate student at Penn State University, and co-first author on this study.

The rest is here:
Science Behind the Scenes: Multiplexed CRISPR and sgRNA Arrays with the Howard Salis Lab | PLOS Synthetic Biology Community - PLoS Blogs

The research report provides valuable insights into demand drivers, geographical outlook, and competitive landscape of the CRISPR and Cas Genes Market over the forecast period. Further, it throws light on restraints as well discusses opportunities at length that are likely to come to the fore over the forecast period. The analysis thus provided helps market stakeholders with business planning and to gauge scope of expansion in the CRISPR and Cas Genes Market over the forecast period.

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The report includes an exhaustive list of top players in the CRISPR and Cas Genes Market are Synthego, Thermo Fisher Scientific, Inc., GenScript, Addgene, Merck KGaA (Sigma-Aldrich), Integrated DNA Technologies, Inc., Transposagen Biopharmaceuticals, Inc., OriGene Technologies, Inc., New England Biolabs, Dharmacon, Cellecta, Inc., Agilent Technologies, and Applied StemCell, Inc.

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Key Questions Answered in the Report

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CRISPR and Cas Genes Market Estimated to Rise at a Lucrative CAGR of 20.1% During 2018-2026 - TheFinanceTime

The CRISPR gene-editing tool can be used to silence an important hepatitisB virus gene, a proof-of-concept invitro study suggests.

"It's the first time we've seen CRISPR editing done in a hepatitisB model," said Douglas Dieterich, MD, director of the Institute of Liver Medicine and professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City.

HepatitisB can lead to liver disease and is the primary cause of hepatocellular carcinoma. In 2015, more than 250million people around the world were infected with the virus, according to the World Health Organization.

For their study, investigator Hao Zhou, from The First Hospital of Jilin University in China and the Department of Medicine at the University of Minnesota in Minneapolis, and colleagues targeted the Sgene. Zhou presented the findings at the Liver Meeting 2019 in Boston.

The Sgene gives rise to the hepatitisB surface antigen, the presence of which indicates that a person is infected with the virus. "The question is whether it's the right target," Dieterich told Medscape Medical News.

Reducing the amount of the hepatitisB surface antigen is a "good idea" because that's what is believed to inhibit the immune system from clearing the virus. Doing so might help the immune system recover and clear the virus, "with a little help from some antivirals," explained Dieterich, who was not involved in the study.

However, "the surface is not the only DNA that's integrated into the host genome," he pointed out. "I think maybe a broader application might be necessary to actually get the hepatitisB genome out of the hepatocytes."

Zhou's team used a newer CRISPR approach, called CRISPR-STOP, for their gene-editing procedure.

"The idea is that CRISPR-STOP can be as efficient as standard CRISPR editing, but it's safer," said Kiran Musunuru, MD, PhD, associate professor of cardiovascular medicine and genetics at Penn Medicine in Philadelphia, who was not involved in the study. Musunuru is cofounder of and senior scientific advisor at Verve Therapeutics, a company using gene editing to prevent cardiovascular disease.

The standard CRISPR-Cas9 approach requires a double-strand break in the genome, and the problem with that is it introduces the possibility for "mischief," he explained. "If you have more than one double-strand break occurring in the human genome at the same time, you have the potential for different parts of different chromosomes coming together in the wrong ways and then causing problems."

Instead of creating a double-strand break, CRISPR-STOP uses a base editor to chemically modify the DNA base from one base to another and introduce a stop codon into the target gene sequence, effectively hamstringing the ability of the target gene to produce a functional protein.

This is a very nice, clean way to turn off a gene effectively.

"This is a very nice, clean way to turn off a gene effectively," Musunuru told Medscape Medical News.

For their CRISPR-STOP procedure, Zhou's team first transduced liver cells infected with the hepatitisB virus using a base editor called AncBE4max. Next, to activate the base editor so that gene editing could begin, they transduced the cells with one of two lentivectors: one encoded for single-guide RNA that targets the Sgene; and an empty one, which served as the control.

With the gene-editing approach, 71% of the liver cells that expressed the base editor gained the desired stop codon in the target gene.

"That's a very robust number," said Musunuru.

In addition, hepatitisB surface antigen secretion was reduced by 92% with the gene-editing approach.

The investigators report a high degree of conservativity for hepatitisB genotypesB, C, F, and H. Specifically, 94% of the Sgene sequence was conserved for genotypeB, 92% for genotypeC, 91% for genotypeF, and 71% for genotypeH.

The Liver Meeting 2019: American Association for the Study of Liver Diseases (AASLD): Abstract86. Presented November10, 2019.

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CRISPR Used to Silence Crucial Hepatitis B Gene - Medscape

New cell experiments show more effective genetic cuts that could one day become the foundation of more effective gene therapies.

Researchers may have found a way to sharpen the CRISPR-Cas9 technique so it can more successfully cut out undesirable genetic information and could one day fast-track potential therapies for HIV, sickle cell disease and, potentially, other immune conditions.

This is the first time scientists have systematically gone through the guide RNA sequence to change it and improve CRISPR-Cas9 technology, said Tristan Scott, PhD, lead author of the study and a staff research scientist at City of Hopes Center for Gene Therapy.

This could lead to more clean results in cell and mouse model experiments aimed at developing new therapies because the target that was knocked out was more successfully removed. More pronounced results could quicken new the development of therapies. In theory, the therapeutic product should have more successful cuts, which could translate into an improved therapy.

The researchers experimented on cells by making changes to the trans-activating CRISPR RNA (or tracrRNA), which is derived from Streptococcus pyogenes bacteria and is a part of the components used to guide the genetic scissors (Cas9) to the right gene sequence.

They found that the modified tracrRNA improved the silencing of certain genes by increasing desirable mutations in the genetic material. In this study, the target was an essential component of HIVs lifecycle, the protein CCR5 on immune CD4+ T cells. The modified tracrRNA improved cutting at this site and inactivation of CCR5, and hopefully that will translate into better protection for the immune system.

The new design was also better at improving activity at the HBB gene and the BCL11A site, both of which are tied to sickle cell disease and are being targeted in order to develop therapies for the currently incurable blood disease that causes intense pain and premature death.

If this line of research remains consistent and we can dependably sharpen the genetic scissor, the result could eventually be new or improved genetic therapies, Scott said.

The study was published inScientific Reports.

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Modified CRISPR gene editing tool could improve therapies - Drug Target Review

New Jersey, NJ, Nov. 13, 2019 (GLOBE NEWSWIRE) -- The key contributing factors for the market growth are increasing demand for enhanced crop varieties using modern breeding techniques and exponential reduction in the cost of genomic solutions. Theglobal plant breeding and CRISPR plants market is expected to grow from USD 6.3 Million in 2017 to USD 21.2 Million by 2025 at a CAGR of 16.4% during the forecast period 2018-2025, according to the new report published by Fior Markets.

The CRISPR-Cas9 system is defined as a plant breeding innovation that uses site-directed nucleases to target and transform DNA with great accuracy. It was developed in 2012 by scientists from the University of California, Berkeley, and has received a lot of focus in recent years due to its wide range of uses, including biological research, breeding and development of crops and animals, and human health applications. It also includes gene silencing, DNA-free CRISPR-Cas9 gene editing, homology-directed repair (HDR), and transient gene silencing or transcriptional repression (CRISPR).

Increasing demand for enhanced crop varieties using modern breeding techniques is a major factor driving the market. Also, exponential reduction in the cost of genomic solutions and advancements in technology ensure strong market growth. High cost associated with modern breeding methods as compared to conventional breeding, poor laboratory infrastructure and lack of validated markers hampers the growth of the market. However, rising investments from seed companies and favourable regulations for molecular breeding may boost the market in the coming years.

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Key players in the plant breeding and CRISPR plants market are Bayer, Syngenta, KWS, DowDuPont, Eurofins, SGS, Advanta Seeds, Benson Hill Biosystems, Bioconsortia, DLF, Equinom, Evogene, Groupe Limagrain, Hudson River Biotechnology, Land Olakes, Pacific Biosciences, SGS, and Syngenta among others. Key players active in the market are involved in collaborative agreements and expansion to bolster the growth of the market.

The hybridization segment held the largest market share of 45.70% in 2017

The process segment is classified into selection, hybridization and mutation breeding. The hybridization segment is dominated the Plant Breeding and CRISPR Plants Market in 2017 with a market share of 45.70%. The most successful applications of hybridization breeding are the utilization of heterosis and generation of seedless horticultural crops, such as watermelon, by employing diploid and tetraploid parents.

Biotechnological method segment valued around USD 3.99 Million in 2017

The type segment includes conventional breeding and biotechnological method. Biotechnological method segment valued around USD 3.99 Million & dominated the market in 2017. The increasing implementation of hybrid and molecular breeding techniques in developing countries and the rising cultivation of GM crops in the Americas are the factors contributing to its high growth.

The herbicide tolerance segment held the largest market share of 36.90% in 2017

Trait segment is divided into segments such as herbicide tolerance, disease resistance, yield improvement and other traits. The herbicide tolerance segment dominated the market in 2017 with a market share of 36.90%. Rising regulations on the use of chemical pesticides and increasing instances of pest attacks during the early germination phase have risen considerably due to the need for pesticide-tolerant seeds.

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The cereals & grains segment valued around USD 2.40 Million in 2017

The application segment includes cereals & grains, oilseeds & pulses, fruits & vegetables and other crop types. The cereals & grains segment valued around USD 2.40 Million and dominated the market in 2017. Corn, wheat, and rice are the major cereals bred with advanced technologies such as molecular breeding and genetic techniques. The availability of germplasm for these crops encourages the adoption of advanced breeding techniques.

Regional Segment Analysis of the Plant Breeding and CRISPR Plants Market

Asia Pacific region dominated the global plant breeding and CRISPR plants market with USD 2.72 Million in 2017. The Asia Pacific region is a major manufacturing hub owing to the ever-increasing demand for commercial seeds in the Asian market aligned with the growing economic growth conditions. Also, seed producers such as Bayer, Monsanto, and Syngenta have been showing increasing interest in tapping this potential market, wherein the companies have been expanding their R&D centres across the Asia Pacific. North America is the second fastest-growing region due to the increasing industrial value for corn and soybean in the US which is encouraging breeders to adopt advanced technologies for better yield, owing to which the adoption rate for genetics in this country remains high.

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The global plant breeding and CRISPR plants market is analysed on the basis of value (USD Million). All the segments have been analysed on global, regional and country basis. The study includes the analysis of more than 30 countries for each segment. The report offers in-depth analysis of driving factors, opportunities, restraints, and challenges for gaining the key insight of the market. The study includes porters five forces model, attractiveness analysis, raw material analysis, supply, demand analysis, competitor position grid analysis, distribution and marketing channels analysis.

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Fior Markets is a futuristic market intelligence company, helping customers flourish their business strategies and make better decisions using actionable intelligence. With transparent information pool, we meet clients objectives, commitments on high standard and targeting possible prospects for SWOT analysis and market research reports. Fior Markets deploys a wide range of regional and global market intelligence research reports including industries like technology, pharmaceutical, consumer goods, food and beverages, chemicals, media, materials and many others. Our Strategic Intelligence capabilities are purposely planned to boost your business extension and elucidate the vigor of diverse industry. We hold distinguished units of highly expert analysts and consultants according to their respective domains. The global market research reports we provide involve both qualitative and quantitative analysis of current market scenario as per the geographical regions segregated and comprehensive performance in different regions with global approach. In addition, our syndicated research reports offer a packaged guide to keep companies abreast of the upcoming major restyle in their domains. Fior Markets facilitates clients with research analysis that are customized to their exact requirements, specifications and challenges, whether it is comprehensive desk research, survey work, composition of multiple methods, in-detailed interviewing or competitive intelligence. Our research experts are experienced in matching the exact personnel and methodology to your business need.

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Global Plant Breeding and CRISPR Plants Market is Expected to Reach USD 21.2 Million by 2025 : Fior Markets - GlobeNewswire

Upon meeting for the first time at a dinner at Stanford earlier this year, Fei-Fei Li and Jennifer Doudna couldnt help but note the remarkable parallels in their experiences as scientists.

Stanfords Fei-Fei Li and Jennifer Doudna of UC Berkeley will discuss the ethics of artificial intelligence and CRISPR technology. (Image credit: Getty Images)

Both women helped kickstart twin revolutions that are profoundly reshaping society in the 21st century Li in the field of artificial intelligence (AI) and Doudna in the life sciences. Both revolutions can be traced back to 2012, the year that computer scientists collectively recognized the power of Lis approach to training computer vision algorithms and that Doudna drew attention to a new gene-editing tool known as CRISPR-Cas9 (CRISPR for short). Both pioneering scientists are also driven by a growing urgency to raise awareness about the ethical dangers of the technologies they helped create.

It was just incredible to hear how similar our stories were. Not just the timing of our scientific discoveries, but also our sense of responsibility for the ethics of the science are just so similar, said Li, who is a professor of computer science at Stanfords School of Engineering and co-director of the Stanford Institute for Human-Centered Artificial Intelligence (HAI).

The ethical angle to what we were doing was not something that either of us anticipated but that we found ourselves quickly drawn to, said Doudna, who is a professor of chemistry and of molecular and cell biology at the University of California, Berkeley.

The echoes between Li and Doudnas lives were also not lost on the dinner host that night, Stanford political science professor Rob Reich, who invited the pair to resume their conversation in public. Their talk, titled CRISPR, AI, and the Ethics of Scientific Discovery, will take place at Stanford on Nov. 19 and will be moderated by Stanford bioengineering professor Russ Altman(livestream will be available here).

The event is organized by the Stanford McCoy Family Center for Ethics in Society and HAI and is part of the Ethics, Society & Technology Integrative Hub that arose from the universitys Long-Range Vision.

The subject of the lecture hits the sweet spot of what the Integrative Hubs work is about, which is to cultivate and support the large community of faculty and students who work at the intersection of ethics, society and technology, said Reich, who directs the Center for Ethics in Society and co-directs the Integrative Hub.

I cant think of two better people to engage in a conversation and to really take seriously these questions of how, as you discover the effects of what youve created, do you bring ethical implications and societal consequences into the discussion? said Margaret Levi, a professor of political science at Stanfords School of Humanities and Sciences. Levi is also the Sara Miller McCune Director of the Center for Advanced Study in the Behavioral Sciences and co-director of the Integrative Hub.

Fei-Fei Li is a professor of computer science and co-director of Stanfords Institute for Human-Centered Artificial Intelligence. (Image credit: L.A. Cicero)

In 2006, Li wondered if computers could be taught to see the same way that children do through early exposure to countless objects and scenes, from which they could deduce visual rules and relationships. Her idea ran counter to the approach taken by most AI researchers at the time, which was to create increasingly customized computer algorithms for identifying specific objects in images.

Lis insight culminated in the creation of ImageNet, a massive dataset consisting of millions of training images, and an international computer vision competition of the same name. In 2012, the winner of the ImageNet contest beat competitors by a wide margin by training a type of AI known as a deep neural network on Lis dataset.

Li immediately understood that an important milestone in her field had just been reached, and despite being on maternity leave at Stanford, flew to Florence, Italy, to attend the award ceremony in person. I bought a last-minute ticket, Li said. I was literally on the ground for about 18 hours before flying back.

Computer vision and image recognition are largely responsible for AIs rapid ascent in recent years. They enable self-driving cars to detect objects, Facebook to tag people in photos and shopping apps to identify real-world objects using a phones camera.

Within a year or so of when the ImageNet result was announced, there was an exponential growth of interest and investment into this technology from the private industry, Li said. We recognized that AI had gone through a phase shift, from being a niche scientific field to a potential transformative force of our industry.

The field of biology underwent its own phase shift in the summer of 2012 when Doudna and her colleagues published a groundbreaking paper in the journal Science that described how components of an ancient antiviral defense system in microbes could be programmed to cut and splice DNA in any living organism, including humans, with surgical precision. CRISPR made genomes as malleable as a piece of literary prose at the mercy of an editors red pen, Doudna would later write.

CRISPR could one day enable scientists to cure myriad genetic diseases, eradicate mosquito-borne illnesses, create pest-resistant plants and resurrect extinct species. But it also raises the specter of customizable designer babies and lasting changes to the human genetic code through so-called germline editing, or edits made to reproductive cells that are transmitted to future generations.

This bioethics nightmare scenario was realized last fall when a Chinese researcher declared that he had used CRISPR to edit the genomes of twin girls in order to make them resistant to HIV. Doudna decried the act but allows that her own views on germline editing are still evolving.

Ive gone from thinking never, ever to thinking that there could be circumstances that would warrant that kind of genome editing, she said. But it would have to be under circumstances where there was a clear medical need that was unmet by any other means and the technology would have to be safe.

Both Li and Doudna fervently believe in the potential of their technologies to benefit society. But they also fear CRISPR and AI could be abused to fuel discrimination and exacerbate social inequalities.

The details are different for CRISPR and AI, but I think those concerns really apply to both, Doudna said.

Rather than just leaving such concerns to others to work out, both scientists have stepped outside of the comfort of their labs and taken actions to help ensure their worst fears dont come to pass. I almost feel that at this point of history I need to do this, not that its my natural tendency, Li said. It really is about our collective future due to technology.

Both scientists have testified before Congress about the possibilities and perils of their technologies. Li also co-launched a nonprofit called AI4All to increase inclusion and diversity among computer engineers and she co-directs Stanford HAI, which aims to develop human-centered AI technologies and applications. Doudna spends significant time talking to colleagues, students and the public about CRISPR. In 2015 she organized the first conference to discuss the safety and ethics of CRISPR genome editing.

Because we were involved in the origins of CRISPR, I felt it was especially important for my colleagues and me to be part of that discussion and really help to lead it, Doudna said. I asked myself, If I dont do it, who will?

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Altman is the Kenneth Fong Professor of Bioengineering, Genetics, Medicine, Biomedical Data Science and host of the Stanford Engineering radio show The Future of Everything. Levi is a member of Stanford Bio-X, the Wu Tsai Neurosciences Institute, and the Stanford Woods Institute for the Environment. Li is the Sequoia Capital Professor at Stanford and a member of Stanford Bio-X and the Wu-Tsai Neurosciences Institute.

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AI and gene-editing pioneers to discuss ethics - Stanford University News

1. CRISPR: the movie  Nature.com
2. CRISPR: More than just for gene editing?  Phys.org
3. Penn Med study on CRISPR cancer therapy indicates technique is safe in humans  The Daily Pennsylvanian
4. Controversial CRISPR gene-editing tool could be used to detect viruses  Daily Mail
5. Crispr Takes Its First Steps in Editing Genes to Fight Cancer  Seattle Times
6. View full coverage on Google News

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CRISPR: the movie - Nature.com

Amended Celgene collaboration to focus on engineered alpha-beta T cell medicines with a $70 million payment to Editas Medicine

Appointed Judith R. Abrams, M.D., as Chief Medical Officer

EDIT-101 (AGN-151587) for LCA10 first patient dosing expected by early 2020

EDIT-301 for hemoglobinopathies in vivo pre-clinical data to be presented at ASH

CAMBRIDGE, Mass., Nov. 12, 2019 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today reported business highlights and financial results for the third quarter of 2019.

"Our momentum in 2019 remains strong in advancing our pipeline of in vivo CRISPR and engineered cell medicines," said Cynthia Collins, Chief Executive Officer of Editas Medicine. We announced this morning an amended agreement with Celgene to further expand and accelerate our oncology pipeline. In hemoglobinopathies, we look forward to presenting in vivo pre-clinical data for EDIT-301 at ASH that supports its potential as a best-in-class medicine. Finally, we eagerly anticipate first patient dosing with EDIT-101 for LCA10 in the coming months.

Recent Achievements and OutlookIn VivoCRISPR Medicines

Engineered Cell Medicines

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Upcoming Events

Editas Medicine will participate in the following investor events:

Editas Medicine will present pre-clinical data for EDIT-301 to address sickle cell disease and beta-thalassemia in at the 61st American Society of Hematology Annual Meeting & Exposition. Details are as follows:

Abstract Number: 4636Title: EDIT-301: An Experimental Autologous Cell Therapy Comprising Cas12a-RNP Modified mPB-CD34+ Cells for the Potential Treatment of SCDPresenter: Edouard De Dreuzy, Ph.D.Session: 801. Gene Therapy and Transfer: Poster III Time: Monday, December 9, 2019: 6:00 PM-8:00 PMLocation: Hall B, Orange County Convention Center, Orlando, FL

Third Quarter 2019 Financial Results

Cash, cash equivalents, and marketable securities at September 30, 2019, were $332.6 million, compared to $369.0 million at December 31, 2018. The $36.4 million decrease was primarily attributable to operating and capital expenses related to our on-going preclinical and clinical activities, patent costs and license fees, and employee-related costs, partially offset by $42.1 million in proceeds from financing activities.

For the three months ended September 30, 2019, net loss was $32.9 million, or $0.66 per share, compared to $15.2 million, or $0.32 per share, for the same period in 2018.

Conference Call

The Editas Medicine management team will host a conference call and webcast today at 8:00 a.m. ET to provide and discuss a corporate update and financial results for the third quarter of 2019. To access the call, please dial 844-348-3801 (domestic) or 213-358-0955 (international) and provide the passcode 6577216. A live webcast of the call will be available on the Investors & Media section of the Editas Medicine website at http://www.editasmedicine.com and a replay will be available approximately two hours after its completion.

About Editas MedicineAs a leading genome editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas9 and CRISPR/Cpf1 (also known as Cas12a) genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision genomic medicines for a broad class of diseases. For the latest information and scientific presentations, please visit http://www.editasmedicine.com.

About EDIT-101 (AGN-151587)EDIT-101 is a CRISPR-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10). EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells.

About Leber Congenital AmaurosisLeber congenital amaurosis, or LCA, is a group of inherited retinal degenerative disorders caused by mutations in at least 18 different genes. It is the most common cause of inherited childhood blindness, with an incidence of two to three per 100,000 live births worldwide. Symptoms of LCA appear within the first years of life, resulting in significant vision loss and potentially blindness. The most common form of the disease, LCA10, is a monogenic disorder caused by mutations in the CEP290 gene and is the cause of disease in approximately 2030 percent of all LCA patients.

About the Editas Medicine-Allergan AllianceIn March 2017, Editas Medicine and Allergan Pharmaceuticals International Limited (Allergan) entered a strategic alliance and option agreement under which Allergan received exclusive access and the option to license up to five of Editas Medicines genome editing programs for ocular diseases, including EDIT-101 (AGN-151587). Under the terms of the agreement, Allergan is responsible for development and commercialization of optioned products, subject to Editas Medicines option to co-develop and share equally in the profits and losses of two optioned products in the United States. In August 2018, Allergan exercised its option to develop and commercialize EDIT-101 globally for the treatment of LCA10. Additionally, Editas Medicine exercised its option to co-develop and share equally in the profits and losses from EDIT-101 in the United States. Editas Medicine is also eligible to receive development and commercial milestones, as well as royalty payments on a per-program basis. The agreement covers a range of first-in-class ocular programs targeting serious, vision-threatening diseases based on Editas Medicines unparalleled CRISPR genome editing platform, including CRISPR/Cas9 and CRISPR/Cpf1 (also known as Cas12a).

Forward-Looking StatementsThis press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, target, should, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements regarding the Companys plans with respect to the Brilliance Phase 1/2 clinical trial for EDIT-101 (AGN-151587), including the Companys expectations regarding the timing of dosing a patient by early 2020. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of pre-clinical studies and clinical trials and clinical development of the Companys product candidates; availability and timing of results from pre-clinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products and availability of funding sufficient for the Companys foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption Risk Factors included in the Companys most recent Quarterly Report on Form 10-Q, which is on file with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.

Investor ContactMark Mullikin(617) 401-9083mark.mullikin@editasmed.com

Media ContactCristi Barnett(617) 401-0113cristi.barnett@editasmed.com

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Editas Medicine Announces Third Quarter 2019 Results and Update - GlobeNewswire

Q&A

Penn's Kiran Musunuru talks to us about the technology that has been both praised and criticized for its ability to alter human DNA and potentially cure disease.

Kiran Musunuru is an associate professor of medicine in genetics in the Perelman School of Medicine at the University of Pennsylvania. / Courtesy

CRISPR, the technology being used to edit genes in humans, remains polarizing. On one end, detractors argue that using the technology for certain purposes, like performing gene editing on embryos, is not only dangerous but unethical. On the other end, proponents say CRISPR has the potential to revolutionize human health, and early data shows they might be right. Despite a medical community that is still split on the issue, researchers in the U.S. are kicking tests of the technology into high gear. Several clinical trials have launched in the U.S. testing CRISPRs ability to treat various diseases.

NextHealth PHL spoke with Kiran Musunuru, an associate professor of medicine in genetics at the Perelman School of Medicine at the University of Pennsylvania about the true potential of CRISPR technology and how we can expect it to evolve in the future.

NextHealth PHL: What exactly is CRISPR?Musunru: CRISPR is sort of a catch-all term that covers a variety of technologies. If youre saying CRISPR, youre referring to a broad set of tools that may do it in different ways but are all intended to do a form of gene editing or genome editing.

How do basic CRISPR technologies work?The simplest form of CRISPR, what I call version 1.0, is the original standard CRISPR that most laboratories and companies interested in developing new therapies use. It is a two-component system. There is a protein and an RNA molecule thats about 100 bases in length. The protein and the RNA molecule come together to create what well call a molecular machine and the purpose of this molecular machine is to scan across any DNA molecule it encounters. So if you put the CRISPR-Cas9 into the nucleus of a human cell, this molecular machine will scan the entire genome.

The machine has two key functions built into it; the first is a GPS function. When you change the first 20 bases in a DNA length (the first 20 bases is basically the address) to whatever address you want, the GPS function makes the machine go through the entire genome and find the sequence that matches the address. The second function of this machine is to protect the genome, like a search-and-destroy function. You put in the address, it goes to that matching place in the genome and then it makes a cut in the DNA.

Cutting the DNA is actually a bad thing but the cells have ways to try to fix that break, and the actual editing is a result of the cell trying to fix that break in the DNA, not from CRISPR itself, interestingly enough.

How does CRISPR turn a break in someones DNA into a good thing?There are a few ways this can happen. The safest thing you can do is to break a gene or turn off a gene. The metaphor I like to use is to think of the whole genome as a book, and each chromosome in the genome is a chapter in the book, and each gene is a paragraph in the chapter. Together, it all has a meaning. But lets say you had to turn off a gene, the equivalent of making that break in the DNA would be like tearing the page through that paragraph. So, the simplest thing the cell can do and will try to do is to simply tape that tear back up. But as you can imagine, sometimes you tape it back up and its fine, the paragraph is still legible and the meaning is still there, and it eventually heals and functions like it did before. But in this case, thats actually not what you want. The outcome that you want with CRISPR is that you actually want to turn off the gene, not to rip it and make it the way it was before.

What has to happen is when you make the tear, the tear is so rough, you get those jagged edges and you try to tape it up but it doesnt quite fit, the letters dont quite match up. You tape it up as best as you can but its illegible, some letters are lost, and the meaning of the paragraph is lost. Thats exactly what happens with gene editing, the cell tries to repair that break in the DNA, doesnt get it quite right, and loses some bases and that messes up the gene and turns it off.

However, in this scenario, you cant really control what happens. All you can hope for is that that tear you make is going to mess up the gene and thats okay if all youre trying to do is turn it off. Most of the trials underway now are about turning off the gene, and theyre all taking advantage of the fact that its relatively easy to mess up genes and turn off genes. Just like tearing a page its crude, but its effective.

Theres CRISPR 1.0, this first generation of the technology thats not very precise and is a bit arduous. What are the newest forms of CRISPR and how are they better than earlier versions of the technology? There is a newer form of the technology called base editing that keeps the GPS function intact but removes the cutting function. In place of the cutting function, it attaches another machine onto CRISPR and makes chemical modifications in certain areas. This version of CRISPR is more like a search and replace. CRISPR provides the search but then another machine attached to it is doing the replacing. With base editing you can make more precise changes, but only rarely will it make exactly the type of change you want.

The latest form of CRISPR is called prime editing, and we still dont have a good sense of how well it works because its so new. Whats tantalizing is that it looks like it can turn CRISPR into a precise word processor or an eraser that allows you to erase a letter and put in a new letter. CRISPR is very much a wave of technology, and as it gets better, its going to allow us to do more and more powerful things.

There are some extreme ideas about what CRISPR can do. Some believe scientists can use the technology to alter hair or eye color or give patients superhuman athletic or intellectual abilities. Is any of this possible with CRISPR?It depends on what traits youre talking about changing. Since eye color and hair color are controlled by single genes, you could possibly make a single gene change with CRISPR. The problem is, how do you get CRISPR to go where it needs to go to change your hair or eye color? How do you get it into all your hair follicles or through all the cells in your eye? It might be a simpler change to make, but it might not be easy to do in a live adult. Scientists have now edited human embryos, resulting in live-born people. Theres been a lot of ethical debate about whether thats a good thing. If you want to change something like hair color in a single cell embryo made through in-vitro fertilization, thats a bit different and might not be as difficult.

There are some very complicated things, like intelligence or athletic ability, that are not going to be easy to change. Youd probably have to change hundreds of genes, and thats not going to happen anytime soon. With CRISPR as it is now, maybe you can change one gene; maybe if you really work at it you can change two genes, but hundreds of genes? Youre not going to be able to do that with CRISPR anytime soon.

What has CRISPR been used to treat so far and what could it be used for in the future?There are multiple trials underway to treat rare liver disorders. More recently CRISPR has been used in clinical trials at Penn where at least three patients have been dosed using CAR T immunotherapy. In this case, theyre trying to make patients cells more effective at fighting cancer. But again, that editing is being done outside the body.

There are some things that seem like they would be difficult to treat, but if its the right type of disease and you can get CRISPR to where you need it to go, it might work. One example is in sickle cell disease. The cells that you need to fix in sickle cell disease are in the bone marrow. Fortunately, bone marrow is relatively straight forward to work with. You take the cells out and edit them with some form of CRISPR outside of the body and then put them back in.

Something like cystic fibrosis would be much harder because it affects the entire surface of potentially multiple organs inside the body. Its much harder to deliver CRISPR to all of those places in the body.

There are two other clinical trials that have started in the U.S. One is from a company called CRISPR Therapeutics to treat sickle cell disease and similar blood disorders. Theres another trial underway to treat a genetic form of blindness and this editing would actually happen inside the body.

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Q&A: Everything You Need to Know About the Future of CRISPR-Cas9 - Philadelphia magazine

Professor Glenn Cohen is a Professor of Law at Harvard Law School. He is also the director of Harvard Law School's Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics, and one of the world's leading experts on the intersections of bioethics and the law. Cohen's current projects relate to big data, health information technologies, reproduction/ reproductive technology, research ethics, organ rationing in law and medicine, health policy, FDA law, translation medicine, and medical tourism. The utilization of CRISPR technology as a gene editing tool has spurred significant debate across the globe. In this interview, we gain insight of Cohen's perspectives on the "CRISPR revolution" and learn about the basic ethical issues surrounding the manipulation of the genome for enhancement.

Molly Campbell (MC): You are one of the leading experts on the intersection of bioethics and the law. Please can you tell us more about this field and the types of cases it addresses?Glenn Cohen (GC): Wherever law, medicine, and ethics intersect, thats where the field and I are. Whether it is the ethics of research, reproductive technologies, genetics, end of life decision-making, mental health, neuroscience, rationing, AI, clinical practice, etc. It is a robust and very exciting field.

MC: Currently, what restrictions apply to the use of CRISPR technology in different cell types and organisms? What applications are scientists not allowed to use CRISPR or other gene-editing technologies for? GC: In lay terms, in the United States an appropriations rider prohibits FDA from considering the use of germline gene editing in human beings. Thus, it is not possible to do a clinical trial or the like of this. Many (perhaps all, it is not clear everywhere) other countries across the world also prohibit in one way or another, but not all regulatory regimes may be as effective.

MC: The work of Jiankui He arguably startled the scientific community. In your opinion, do you think the publication of He's work prompted authorities to address regulating CRISPR technology? Or was there already a conversation taking place?GC: There was very robust conversation long before Dr. Hes terrible (and in my view completely unethical) experiments. For example, this report from the National Academies. While CRISPR is relatively new in terms of technology, in fact bioethicists have been talking about the basic issues surrounding manipulating the genome for enhancement for at least 40 years if not longer.

MC: There are concerns that the CRISPR tool could be used for enhancement purposes. In recent opinion article you say, "Anyone who has a position on enhancement has not thought deeply enough on the question." Please can you expand on what you mean by this?

GC: My claim is that enhancement is not a single monolithic thing, so it is hard to have a single position on it. Some enhancements would be wonderful and perhaps the state should subsidize them. Others would be terrible and perhaps the state should prohibit. Only when we think about it with some specificity can we know what we think the answer should be. In the article you mention I draw the following distinctions, for example, though others are possible:

1. Biological vs. Non-Biological Enhancement

a. Genetic enhancements vs. non-genetic biological enhancements

2. Choosing for Ourselves vs. Choosing for Others Who Cannot Choose for Themselvesa. Enhancing after birth vs. enhancing before birthi. Enhancing by selection vs. enhancing by manipulation of already fertilized embryos or implanted fetuses

3. Enhancements Compatible with Expanding Life Plans vs. Enhancements That Will Limit Options

4. Reversible vs. Irreversible Enhancement

5. Some would distinguish enhancement from treatment (though others are skeptical about this distinction)a. Enhancements to the upper bounds of what people already have vs. enhancements that add beyond human nature as it now stands

6. Enhancements for Absolute vs. Positional Goods

MC: A novel community of gene-editing "biohackers" has emerged in the rise of CRISPR technology. What are your opinions of biohackers conducting gene-editing experiments from their homes, from a legal and ethical perspective?GC:I think the community is very interesting. I am a huge fan of open science and the building of intellectual communities. I think the key question is whether/when the work undertaken by this community could pose significant externalities for others. Thats probably where I would start to get concerned.

MC: How do we approach implementing a global legal and ethical framework for using gene-editing technologies? What progress has been made thus far?GC: The WHO has chartered an advisory committee which has recommended a registry of all those doing gene editing work and has advised that it is irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing." I think the existence of this committee (alongside the NASEM, Nuffield Council) and others working on these issues is a great step.

My own view is that we ought to be looking for a responsible translational pathway that might allow some clinical work to be reviewed and approved by regulators like the FDA in the future, but certainly there is nothing there yet. The international aspect makes this very, very difficult. Some have suggested we ought to go for an international treaty, like what we have on landmines and chemical weapons but also recognition of adoption, while others think this is infeasible.

MC: What challenges exist when looking to create laws surrounding a novel scientific technology?GC: There are quite a few. The first is uncertainty whenever you move to first-in-humans, whatever pre-clinical work you have done, there is always open questions. The same was true with IVF. The second is the politicization of science and the reduction of difficult and nuanced questions to talking points. The third is deep philosophical disagreement on some key points (for example, some take quite literally the idea of "man created in Gods image" and view altering the human genome as a rejection of that. If thats what someone believes for religious reasons then it is very hard to talk about these issues at a more policy level). Fourth, is the importance but difficult of public engagement. The UK in its public consultation on mitochondrial replacement therapy (that ultimately paved the way for permitting that technology to be used in a limited way) was a very good recent model, but quite difficult and expensive. Moreover, some felt it didnt go far enough in the direction of deliberative democracy. The hope is we will see more such initiatives for gene editing and other novel technologies.

Professor Glenn Cohen, Haravard Law School, was speaking with Molly Campbell, Science Writer, Technology Networks.

Catch up on the previous instalment of Technolology Networks Explores the CRISPR Revolution, an interview with Professor George Church, here.

See the original post:
Technology Networks Explores the CRISPR Revolution: An Interview With Professor Glenn Cohen, World-leading Expert on Bioethics - Technology Networks

The first attempt in the United States to use a gene editing tool called CRISPR against cancer seems safe in the three patients who have had it so far, but its too soon to know if it will improve survival, doctors reported Wednesday.

The doctors were able to take immune system cells from the patients blood and alter them genetically to help them recognize and fight cancer, with minimal and manageable side effects.

The treatment deletes three genes that might have been hindering these cells ability to attack the disease, and adds a new, fourth feature to help them do the job.

Its the most complicated genetic, cellular engineering thats been attempted so far, said the study leader, Dr. Edward Stadtmauer of the University of Pennsylvania in Philadelphia. This is proof that we can safely do gene editing of these cells.

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After two to three months, one patients cancer continued to worsen and another was stable. The third patient was treated too recently to know how shell fare. The plan is to treat 15 more patients and assess safety and how well it works.

Its very early, but Im incredibly encouraged by this, said one independent expert, Dr. Aaron Gerds, a Cleveland Clinic cancer specialist.

Other cell therapies for some blood cancers have been a huge hit, taking diseases that are uncurable and curing them, and the gene editing may give a way to improve on those, he said.

Gene editing is a way to permanently change DNA to attack the root causes of a disease. CRISPR is a tool to cut DNA at a specific spot. Its long been used in the lab and is being tried for other diseases.

This study is not aimed at changing DNA within a persons body. Instead it seeks to remove, alter and give back to the patient cells that are super-powered to fight their cancer a form of immunotherapy.

Chinese scientists reportedly have tried this for cancer patients, but this is the first such study outside that country. Its so novel that it took more than two years to get approval from U.S. government regulators to try it.

The early results were released by the American Society of Hematology; details will be given at its annual conference in December.

The study is sponsored by the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy in San Francisco, and a biotech company, Tmunity Therapeutics. Several study leaders and the university have a financial stake in the company and may benefit from patents and licenses on the technology.

Two of the patients have multiple myeloma, a blood cancer, and the third has a sarcoma, cancer that forms in connective or soft tissue. All had failed multiple standard treatments and were out of good options.

Their blood was filtered to remove immune system soldiers called T cells, which were modified in the lab and then returned to the patients through an IV. Its intended as a one-time treatment. The cells should multiply into an army within the body and act as a living drug.

So far, the cells have survived and have been multiplying as intended, Stadtmauer said.

This is a brand new therapy so not its not clear how soon any anti-cancer effects will be seen. Following these patients longer, and testing more of them, will tell, he said.

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See more here:
Doctors try CRISPR gene editing for cancer, a 1st in the US - NBCNews.com

A team of scientists from City University of Hong Kong (CityU) and the Karolinska Institute has created a novel protein that can increase the target accuracy in genome editing. Their findings are published in the journal Proceedings of the National Academy of Sciences (PNAS).Meet CRISPRThe gene editing technology Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 looks set to revolutionize modern medicine, agriculture, and synthetic biology.The ability to edit the genome in vivo offers the potential to develop novel gene therapies for diseases that currently lack viable treatment options. Several clinical trials are underway exploring the utility of CRISPR technology in treating specific cancers, blood disorders and eye diseases.CRISPR-Cas9 as a gene editing tool is superior over other techniques due to its ease of use. In traditional gene therapy, additional copies of the "normal" gene are introduced into cells. Using CRISPR technology, this isnt necessary; CRISPR-Cas9 enters the cell and "repairs" the problematic gene by removing it or correcting it to restore normal physiological function.

There are different components to the CRISPR mechanism. Cas9 is the enzyme that flags and locates the problematic DNA throughout the genome, acting in a "hunting" fashion. However, the precision of Cas9 cannot always be established, and occasionally modifications of DNA at unintended places can occur. If CRISPR is to be utilized to repair faulty genes in patients, potential off-target genome editing could have serious adverse effects.

There are currently two versions of the Cas9 enzyme commonly adopted in CRISPR research: SpCas9 (Cas9 nuclease from the bacteria Streptococcus pyogenes) and SaCas9 (Cas9 nuclease from Staphylococcus aureus). Both of these enzymes are limited in that they possess a certain level of imprecision.

Thus, scientists have endeavored to develop variants of both enzymes, with the aim being to increase their precision and reduce off-target effects. The issue with SpCas9 is that the modified variants are often too large to "fit" in the delivery system adopted for inserting gene therapies into patients, known as adeno-associated viral (AAV) vectors.SaCas9 is advantageous over SpCas9 in that it can be easily packaged into the AAV vectors for delivering gene-editing contents in vivo. However, at present, there is no SaCas9 variant that possesses high accuracy in genome-wide editing. Until now.Now meet SaCas9-HFIn the new study published in Proceedings of the National Academy of Sciences (PNAS), a research team led by Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of the Karolinska Institute in Hong Kong, and Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU, has successfully engineered SaCas9-HF, a CRISPR Cas9 variant which has demonstrated high accuracy in genome-wide targeting in human cells without compromising on-target efficiency.In the study, the scientists conducted an extensive evaluation of 24 targeted human genetic locations comparing the original (known as wild-type) SaCas9, and the new variant, SaCas9-HF. They discovered that for targets with highly similar sequences in the genome (and therefore often disposed to off-target editing by wild-type Cas9), SaCas9-HF decreased the off-target activity by ~90%. When assessing targets that had relatively less off-targeting editing by wild-type SaCas9, the SaCas9-HF enzyme produced little to no detectable off-target effects.

"Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing 'drug' in vivo and would be compatible with the latest 'prime editing' CRISPR platform, which can 'search-and-replace' the targeted genes," said Dr Zheng.Reference: Tan et al. 2019. Rationally engineered Staphylococcus aureus Cas9 nucleases with high genome-wide specificity. Proceedings of the National Aacademy of Sciences (PNAS). DOI: https://doi.org/10.1073/pnas.1906843116

Read the rest here:
A Highly Precise Cas9 Enzyme, SaCas9-HF, Is Added to the CRISPR Toolbox - Technology Networks

All right, lets do this one last time. My name is CRISPR. I was made from a bacterial defense system, and for years Ive been the one and only gene editing wunderkind. Im pretty sure you know the rest. Im relatively cheap to make, easy to wield, and snip out genes pretty on target. Im going into clinical trials. Im reviving the entire field of gene therapy. Theres only one CRISPR. And youre looking at it.

Well, just as Spider-Man was way off, so is the idea of a single CRISPR to rule them all. This month, Dr. David Liu at the Broad Institute of MIT and Harvard in Cambridge, MA, introduced an upgrade that in theory may correct nearly 90 percent of all disease-causing genetic variations. Rather than simply deactivating a gene, CRISPR-based prime editing is a true search-and-replace editor for the human genome. With a single version, it can change individual DNA letters, delete letters, or insert blocks of new letters into the genome, with minimal damage to the DNA strand.

For now, prime editing has only been tested in cultured cells. But its efficacy is off the charts. Early experiments found it could correct single-letter misspellings in sickle cell disease, snip out four superfluous letters that underlie Tay-Sachs, and insert three missing letters to correct a genomic typo that leads to cystic fibrosis. In all, the tool worked remarkably well in over 175 edits in both human and mouse cells.

The excitement has been palpable, said Dr. Fyodor Urnov at the University of California, Berkeley, who was not involved in the research. I cant overstate the significance of this.

Given all of the existing CRISPR upgrades, why are scientists head over heels about prime editing?

CRISPR 1.0 generally refers to the classic version, which snips open the double helix to get rid of a certain gene. But as a tool, todays CRISPR is less like genetic scissors and more similar to a Swiss Army knife, one that scientists keep on improving. There are variants that, rather than destroying a gene, insert one or change one genetic letter to another, or ones that can target thousands of genetic spots at the same time. There are also spin-offs that hunt down RNAthe messenger that carries DNAs genetic code to the greater cellular universe, rather than the genetic code itself. Its truly a CRISPR multiverse out there.

Yet for all of CRISPRs upgrades, the tool has serious issues. For one, its very rough on the genome. Cas9, the protein scissor component of CRISPR, doesnt surgically cut out a gene. Rather, editing is in fact the cell detecting damage to the double helix, and trying its best to patch the broken strands back up. Just as scars form on our skin, this process can often introduce errors in the repairing processadding or missing a letter or two. Scientists often take advantage of this botched repair to destroy a gene that causes disease, or sneak in some additional code.

The problem? This process is basically genome vandalism, said Dr. George Church, a CRISPR pioneer at Harvard who wasnt involved in the new work. Its great when the repair goes according to plan; when it doesnt, the repair can introduce unwantedor downright dangerousmutations.

Lius idea for prime editing grew from his work on base editors. Here, the CRISPR machinery doesnt chop up the double helix. Rather, it uses the blood hound guide RNA to shuttle a new protein component to the target DNA sequence. This component then performs a single letter swap: C to T, or G to A.

Although considered much safer than traditional cut-and-glue CRISPR, base editors are limited in the number of genetic diseases they can treat. Its like editing on a broken keyboardsome misspellings just cant be fixed.

Prime editing circumvents these problems by heavily upgrading both components. The altered Cas9, for example, only snips a single strand of the double helix, rather than chomping through both. The new guide, pegRNA, both tethers the entire machinery to the target site, and encodes the desired edit.

Then comes the third component that magically ties everything together: a protein dubbed reverse transcriptase, which can make DNA sequences based on the blueprint in pegRNA, to insert into the nicked target site.

Still confused? Picture the DNA double helix as a laddertwo strands with connecting rungs in the middle. Prime editing cuts one strand using its neutered Cas9. This creates an opening for the other two components to insert a new gene into the severed spot; meanwhile, the original DNA sequence is snipped off. Now, rather than the original X, X (for example), the cell has X, Y.

The prime editor then performs a second snip at the opposing, non-edited strand. This alerts the cell of DNA damage, which it then tries to fixusing the new gene as a template. The end result is the cell goes from disease-causing X, X to normal, healthy Y, Y.

Several reasons.

One, because it doesnt cut both DNA strands, it doesnt immediately activate the cells repair system that is prone to errors. This means that scientists have far better control over the type of edit they want, and its no longer left to chance.

Two, prime is remarkably multi-purpose. Previously, the consensus among genome scientists was that a separate CRISPR tool was required for each specific type of edit: delete a gene, insert new DNA code, or DNA letter substitutions. In contrast, prime can achieve all three functions without additional modification. For experiments, it means less setup. For development into gene therapy, it means less overhead investment.

Three, prime editing can swap any of the DNA letters into any other, meaning it can now target an enormous amount of inherited diseases. For example, sickle cell disease, which causes oxygen-carrying blood cells to deform into sharp sickle-like shapes, requires changing a T into an A at a precise spot. Base editors cant do that. Prime editing can. Thats about 7,000 genetic disorders now amenable to gene therapy.

Four, prime editing also works in cells that no longer divide to renew themselves, such as neurons and muscle cells. Because these cells cant pass on their therapeutic DNA edit to daughter cells, to fix genetic deficits scientists have to be able to efficiently correct mutations in a large population. With prime editing, thats now possible.

Finally, prime editing can remove an exact number of letters from a given spot on the genome, at least up to 80. This allows scientists to precisely dictate the DNA sequences they want out, rather than relying on chance.

Early experiments with prime editing in cells show the tool is incredibly accurate. Off-target nicks were below 10 percent, and less than one-tenth of edited cells had unwanted changes to their genome, compared to up to 90 percent for first-gen CRISPR systems.

Nevertheless, the tool will have to go through rigorous testing before its widely accepted. Working in a few types of human cells is one thing; having it perform equally well inside a living body is something else completely. Most of primes tricks so far can be replicated using CRISPR 1.0, though at lower efficacy and with higher chances of off-target failures. Unlike prime editing, however, the original version has years of experience and plenty of clinical trials underwaycongenital blindness, sickle cell diseaseto back it up.

Whats more, prime is massive in terms of molecular tools. Getting it into cells will be a struggle. Getting it to the brain, which is protected by a dense wall of cells, will be even harder. To get the editor to their target, scientists will likely rely on gene therapy, itself a budding industry.

If CRISPR is like scissors, base editors are like a pencil. Then you can think of prime editors like a word processor, capable of precise search and replace, said Liu. All will have rolesThis is the beginning rather than the end.

Image Credit:petarg/Shutterstock.com

More:
Everything You Need to Know About Superstar CRISPR Prime Editing - Singularity Hub

What happened

Shares of Crispr Therapeutics (NASDAQ:CRSP) jumped nearly 23% last month, according to data provided by S&P Global Market Intelligence. The biopharmaceutical company announced a quarterly update demonstrating multiple areas of progress. The lead drug candidate, CTX001, is enrolling patients at six global sites for a phase 1/2 trial in transfusion-dependent beta thalassemia (TDT) and at 10 global sites for a phase 1/2 trial in sickle cell disease. Preliminary results are expected to be released before the end of 2019, which could have a profound effect on the pharma stock.

The gene-editing pioneer ended September with nearly $630 million in cash, which will come in handy next year when the company expects to have up to five clinical trials ongoing simultaneously. That includes plans to initiate the first clinical trial of CTX120 as a treatment for multiple myeloma in the first half of 2020, which should be followed by multiple trials involving CTX130 in solid tumors and white blood cell cancers.

Image source: Getty Images.

It's certainly difficult for investors to argue against the continuous execution of Crispr Therapeutics. The company was the first using CRISPR gene-editing technology to enter clinical trials, continues to advance multiple assets through the rigors of preclinical work and closer to the clinic, and partners with outside companies to augment its own capabilities. There's the highly visible partnership with Vertex Pharmaceuticals for CTX001 and other pipeline assets, but that's far from the only collaboration.

Crispr Therapeutics previously created a joint venture with Bayer, called Casebia Therapeutics, although control of the start-up will revert to Crispr before the end of 2019. Casebia will focus on programs in hemophilia, eye disorders, and autoimmune diseases. Bayer will have opt-in rights for multiple drug candidates.

Crispr is also collaborating with ViaCyte to develop a cellular medicine for treating type 1 diabetes, and with KSQ Therapeutics to develop CAR-T drug candidates with enhanced allogeneicity (read: grown from a single cell line and able to be used in any individual, in contrast to the strict donor matching required for current CAR-T medicines).

There's a long way to go before the company proves CRISPR gene editing can live up to the hype in human therapeutics, but the pioneer is the best positioned among its peer group. While there are major flaws with CRISPR gene editing that could keep the initial tools from ever being commercialized, Crispr Therapeutics is taking a "softer" approach with ex vivo engineering of white blood cells in blood disorders and for immuno-oncology. Whether the approach yields success remains to be seen, but investors will get their first glimpse of the potential when preliminary results from CTX001 trials are announced in the coming months.

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Here's Why Crispr Therapeutics Gained 22.8% in October - Motley Fool

REPORTING FOR 2019-11-08 | WCX19.ORG: We have done an in-depth analysis of how YGYI has been trading over the last 2 weeks and the past day especially. On its latest session, Youngevity International, Inc. ($YGYI) opened at 4.17, reaching a high of 4.3645 and a low of 4.17 before closing at a price of 4.28. There was a total volume of 40813.

VOLUME INDICATORS FOR YOUNGEVITY INTERNATIONAL, INC. ($YGYI): We saw an accumulation-distribution index of 48.46941, an on-balance volume of -4.21, chaikin money flow of 1.0 and a force index of 0.01053. There was an ease of movement rating of -0.00099, a volume-price trend of -0.48511 and a negative volume index of 1000.0.

VOLATILITY INDICATORS FOR YOUNGEVITY INTERNATIONAL, INC. ($YGYI): We noted an average true range of 0.19856, bolinger bands of 4.18124, an upper bollinger band of 4.14646, lower bollinger band of 4.17, a bollinger high band indicator of 1.0, bollinger low band indicator of 1.0, a central keltner channel of 4.23483, high band keltner channel of 4.04033, low band keltner channel of 4.42933, a high band keltner channel indicator of 1.0 and a low band keltner channel indicator of 1.0. There was a donchian channel high band of 4.17, a donchian channel low band of 4.17, a donchian channel high band indicator of 1.0, and a donchian channel low band indicator of 1.0.

TREND INDICATORS FOR YOUNGEVITY INTERNATIONAL, INC. ($YGYI): We calculated a Moving Average Convergence Divergence (MACD) of -0.00028, a MACD signal of -0.00015, a MACD difference of -0.00012, a fast Exponential Moving Average (EMA) indicator of 4.17, a slow Exponential Moving Average (EMA) indicator of 4.17, an Average Directional Movement Index (ADX) of unknown, an ADX positive of 20.0, an ADX negative of 20.0, a positive Vortex Indicator (VI) of 1.0, a negative VI of 1.0, a trend vortex difference of 0.1596, a trix of -7.37562, a Mass Index (MI) of 1.0, a Commodity Channel Index (CCI) of 66.66667, a Detrended Price Oscillator (DPO) of 0.55384, a KST Oscillator (KST) of -117.24453 and a KST Oscillator (KST Signal) of -117.24453 (leaving a KST difference of -0.65095). We also found an Ichimoku rating of 4.26725, an Ichimoku B rating of 4.26725, a Ichimoku visual trend A of 4.84938, an Ichimoku visual trend B of 4.712, an Aroon Indicator (AI) up of 4.0 and an AI indicator down of 4.0. That left a difference of -4.0.

MOMENTUM INDICATORS FOR YOUNGEVITY INTERNATIONAL, INC. ($YGYI): We found a Relative Strength Index (RSI) of 50.0, a Money Flow Index (MFI) of 34.96838, a True Strength Index (TSI) of -100.0, an ultimate oscillator of -54.12626, a stochastic oscillator of 100.0, a stochastic oscillator signal of 100.0, a Williams %R rating of 1326.2069 and an awesome oscillator of 0.04847.

RETURNS FOR YOUNGEVITY INTERNATIONAL, INC. ($YGYI): There was a daily return of -11.72445, a daily log return of -0.2954 and a cumulative return of -0.29496.

What the heck does all of this mean? If you are new to technical analysis, the above may be gibberish to you, and thats OK (though we do advise learning these things). The bottom line is that AS OF 2019-11-08 (if you are reading this later, the analysis will be out of date), here is what our deep analysis of technical indicators are telling us for Youngevity International, Inc. ($YGYI)

DISCLAIMER: We are not registered investment advisers and the above analysis should be taken at face value only. We strongly advise against buying or selling Youngevity International, Inc. ($YGYI) based solely on our analysis above, and are not responsible for any losses that you may incur if you choose make any investment decisions based on the above.

Continued here:
CRISPR Therapeutics AG ($CRSP): Caution Is Advised (2019-11-08) - WCX19

CRISPR has been making waves with its success in fighting rare genetic diseases, but could it also help turn bacteriums machinery against itself? In the era of superbugs, scientists are hopeful the technology can be a game-changer. Meanwhile, GSK has announced a late-stage study for its new antibiotic to fight urinary tract infections and gonorrhea.

The New York Times:Is Crispr The Next Antibiotic?For decades, scientists and doctors have treated common bacterial and viral infections with fairly blunt therapies. If you developed a sinus infection or a stomach bug, you would likely be given a broad-spectrum antibiotic that would clear out many different types of bacteria. Antiviral drugs help treat viral illnesses in much the same way, by hindering the pathogens ability to reproduce and spread in the body. (Sheikh, 10/28)

Reuters:GlaxoSmithKline Starts Late-Stage Trial For Experimental AntibioticGlaxoSmithKline Plc said on Monday it has begun a late-stage study testing its experimental antibiotic in patients with urinary tract infection and gonorrhoea, a type of sexually transmitted infection. The antibiotic, gepotidacin, is the first of a new class of drugs and is expected to treat the two common infections caused by bacteria - identified as antibiotic resistant threats by U.S. health regulators. (10/28)

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Could CRISPR Technology Rise As A Hero In The Era Of Antibiotic Resistance? - Kaiser Health News

Recently, there has been a shift in societys view of genetic modification and its potential applications in the fight against climate change. This has led to a call for changes in our current policies from farmers and MPs alike. However, due to the Green Partys current stance on this topic, New Zealand is unable to utilise genetic modification for anything that is not laboratory-based.

I am a member of the Emerging Scientists for Climate Action society, which involves students from universities all over New Zealand. We are writing an open letter to the Greens to encourage them to review their stance on genetic modification and the current laws and regulations around genetic engineering. Our overarching goal to tackle climate change aligns with the Greens, and they are in a position to make positive change. We have 155 signatures from emerging scientists (aged under 30) in support.

[Editors note: Deborah Paull is studying for a Masters of Science in Microbiology at the University of Canterbury.]

Genetic modification is a controversial topic, and there is much misunderstanding about its techniques and applications. Genetic modification (aka genetic engineering) uses gene editing technologies and knowledge of genetics to make changes in an organism for a specific outcome. For example, a plant could be genetically modified to grow bigger to produce a higher yield.

Read full, original article: Time to break the stigma on genetic modification, for the sake of the climate

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Young scientists urge New Zealand's Green Party to embrace CRISPR for 'sake of the climate' - Genetic Literacy Project

CRISPR Therapeutics AG (CRSP) came out with quarterly earnings of $2.40 per share, beating the Zacks Consensus Estimate of a loss of $0.95 per share. This compares to loss of $1.07 per share a year ago. These figures are adjusted for non-recurring items.

This quarterly report represents an earnings surprise of 352.63%. A quarter ago, it was expected that this company would post a loss of $0.81 per share when it actually produced a loss of $1.01, delivering a surprise of -24.69%.

Over the last four quarters, the company has surpassed consensus EPS estimates just once.

CRISPR Therapeutics AG, which belongs to the Zacks Medical - Biomedical and Genetics industry, posted revenues of $211.93 million for the quarter ended September 2019, surpassing the Zacks Consensus Estimate by 3,252.23%. This compares to year-ago revenues of $0.56 million. The company has topped consensus revenue estimates just once over the last four quarters.

The sustainability of the stock's immediate price movement based on the recently-released numbers and future earnings expectations will mostly depend on management's commentary on the earnings call.

CRISPR Therapeutics AG shares have added about 39.5% since the beginning of the year versus the S&P 500's gain of 20.6%.

What's Next for CRISPR Therapeutics AG?

While CRISPR Therapeutics AG has outperformed the market so far this year, the question that comes to investors' minds is: what's next for the stock?

There are no easy answers to this key question, but one reliable measure that can help investors address this is the company's earnings outlook. Not only does this include current consensus earnings expectations for the coming quarter(s), but also how these expectations have changed lately.

Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions. Investors can track such revisions by themselves or rely on a tried-and-tested rating tool like the Zacks Rank, which has an impressive track record of harnessing the power of earnings estimate revisions.

Ahead of this earnings release, the estimate revisions trend for CRISPR Therapeutics AG was mixed. While the magnitude and direction of estimate revisions could change following the company's just-released earnings report, the current status translates into a Zacks Rank #3 (Hold) for the stock. So, the shares are expected to perform in line with the market in the near future. You can see the complete list of today's Zacks #1 Rank (Strong Buy) stocks here.

It will be interesting to see how estimates for the coming quarters and current fiscal year change in the days ahead. The current consensus EPS estimate is -$0.98 on $6.58 million in revenues for the coming quarter and -$3.85 on $13.83 million in revenues for the current fiscal year.

Investors should be mindful of the fact that the outlook for the industry can have a material impact on the performance of the stock as well. In terms of the Zacks Industry Rank, Medical - Biomedical and Genetics is currently in the top 29% of the 250 plus Zacks industries. Our research shows that the top 50% of the Zacks-ranked industries outperform the bottom 50% by a factor of more than 2 to 1.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free reportCRISPR Therapeutics AG (CRSP) : Free Stock Analysis ReportTo read this article on Zacks.com click here.Zacks Investment Research

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CRISPR Therapeutics AG (CRSP) Q3 Earnings and Revenues Surpass Estimates - Yahoo Finance

CAMBRIDGE, Mass.--(BUSINESS WIRE)--KSQ Therapeutics, a biotechnology company using CRISPR technology to enable the companys powerful discovery engine to achieve higher probabilities of success in drug development, today announced two upcoming presentations at leading scientific immuno-oncology congresses. The data demonstrate the capabilities of the companys proprietary CRISPRomics discovery engine, which allows genome-scale, in vivo validated, unbiased drug discovery.

There is a significant need for next-generation immuno-oncology therapies as the majority of cancer patients today experience an insufficient response to PD-1/PD-L1 therapies. The data we will be sharing demonstrate the potential of our CRISPRomics discovery platform to systematically identify and validate new cancer therapies for patients with PD-1 refractory solid tumors, said Frank Stegmeier, Ph.D., Chief Scientific Officer at KSQ Therapeutics. KSQ was founded on the premise that CRISPR-enabled functional genomics can improve on current approaches to drug discovery and, taken together, these poster presentations describing the output of our genome-scale in vivo T-cell screens show that our platform can do this with a high degree of precision and quality, pointing the direction towards promising avenues of drug development.

Presentations include:

About KSQ Therapeutics

KSQ Therapeutics is using CRISPR technology to enable the companys powerful discovery engine to achieve higher probabilities of success in drug development. The company is advancing a pipeline of tumor- and immune-focused drug candidates for the treatment of cancer, across multiple drug modalities including targeted therapies, adoptive cell therapies and immuno-therapies. KSQs proprietary CRISPRomics discovery engine enables genome-scale, in vivo validated, unbiased drug discovery across broad therapeutic areas. KSQ was founded by thought leaders in the field of functional genomics and pioneers of CRISPR screening technologies, and the company is located in Cambridge, Massachusetts. For more information, please visit the companys website at http://www.ksqtx.com.

Original post:
KSQ Therapeutics to Present First Data from its Proprietary CRISPRomics Discovery Engine - Business Wire