Genetherapy

Bone Marrow Drive For Allums Siblings At ULM – MyArkLaMiss (press release) (blog)

May 1st, 2017

MONROE, LA - A bone marrow drive for 21-year-old James Christopher Allums and his 3-year-old sister Elizabeth is taking place today, May 1st, at locations throughout Northeast Louisiana.

University of Louisiana Monroe Medical Laboratory Science faculty and students are helping organize the drive. The drive on campus is 9 a.m. to 5 p.m. in the Student Union Building and Quad.

May 1st is National Fanconi Anemia Day. James Christopher and Elizabeth suffer from this disease, which is fatal without a bone marrow or stem cell transplant. They are the children of Chris and Ellen Allums.

Melanie Chapman, assistant professor to the School of Health Professions, said, "This is a wonderful opportunity for ULM Warhawks to fly high by working together and setting aside our busy agendas to give two great kids, and possibly others, the chance to live out their years. I am privileged to be a part of ULM and this community effort."

Bone marrow drive locations:

Times vary and new locations may be added. For information, visit caringbridge.org and search James Christopher Allums .

Here is the original post:
Bone Marrow Drive For Allums Siblings At ULM - MyArkLaMiss (press release) (blog)

Recommendation and review posted by simmons

Benefit planned May 5-6 for area leukemia victim – SalemNews.net

May 1st, 2017

A benefit rummage, bake and vendor sale will be held this Friday and Saturday for Trisha Suits, a Lisbon resident battling leukemia. She is shown with her mother, Alice Loy, and 6-year-old son Landon who proudly displays the jacket Trisha wore while serving as an assistant cross country coach at Lisbon. Despite being virtually blind, the David Anderson High School graduate ran cross country in high school. (Salem News photo by J.D.Creer)

WHAT: Rummage, bake and vendor sale to benefit area resident Trisha Suits who will be undergoing leukemia treatments at the Cleveland Clinic.

WHEN: From 9 a.m.-4 p.m. Friday and Saturday, May 5-6.

WHERE: Guilford Lake Ruritan Hall, state Route 172.

She was born weighing just a pound and eight ounces. But Trisha Suits is hardly a lightweight.

The courageous 30-year-old Lisbon resident, left virtually blind due to her premature birth, has taken on all comers throughout her life. Despite having only 2 percent vision in her right eye and none in her left, she has been a capable mom in helping to raise her son. She is a 2006 David Anderson High School graduate. Remarkably, she ran as a member of the cross-country team, memorizing her routes. Just putting one foot in front of the other, Trisha quipped, saying never fell. She later served as a Blue Devils assistant coach.

Now she is confronting her biggest challenge. She has been diagnosed with a complex form of leukemia and will be undergoing bone marrow and stem cell transplants at the Cleveland Clinic. Due to ongoing treatments, she will be required to remain in the hospital for six weeks. Then she will need to stay at a nearby housing complex for another 100 days.

Trisha was diagnosed in early March, after passing out from severe blood loss. She spent a month in the Cleveland Clinic getting chemotherapy. But due to genetic mutations, she needs bone marrow and stem cell transplants to combat acute myeloid leukemia a type of cancer that starts in the blood-forming cells of marrow.

According to her aunt, Melody Hobbs of Salem, her lengthy stay at the housing complex the Transplant House of Cleveland will cost about $75 per day for just the lodging. A donor has been found. Transplant treatments are expected to begin May 11.

To help offset the costs, a combination rummage, bake and vendor sale for Trisha will be held this Friday and Saturday, May 5-6, from 9 a.m. to 4 p.m. each day at the Guilford Ruritans Hall off of state Route 172.

We just need people to come, Hobbs said. We are trying to raise awareness to get more people out there. All the money raised will pay for Trishas lodging and transportation.

Trishas ordeal is and will continue to be grueling. Admittedly, she gets bitter, angry and frustrated. The uncertainty is overwhelming.

The really hard part of it will be being in Cleveland away from her son and family, said Hobbs.

Indeed, Trishas said her hobby is being the best mom she can be for her son. Six-year-old Landon is a McKinley Elementary School student.

I love my mommy, he offered. Its not just my moms fight, its our fight.

Trisha and her son lives with her parents, Rick Joy and Alice Loy. Her sister, Summer Burkholder, is a co-organizer of this weekends benefit.

The transplants offer a possible cure. Without them, it would be dire.

God only gives me what I can handle, said Trisha who has spent her entire life combating challenges. But I am scared about what this is going to do to my body.

Ongoing updates on Trisha may be found on Facebook. Visit: Trishas Fight with AML. To make an online donation, a link: youcaring.com may be accessed.

jdcreer@salemnews.net

LISBON A Center Township resident believes township trustees should consider banning marijuana facilities of ...

LISBON The company interested in reopening a Middleton Township youth residential treatment home intends to ...

Ohio House Speaker Clifford Rosenberger recently appointed state Rep. Tim Ginter to the Ohio Commission on ...

LEETONIA Grades kindergarten through second at Leetonia Elementary will benefit from a literacy collaborative ...

See the article here:
Benefit planned May 5-6 for area leukemia victim - SalemNews.net

Recommendation and review posted by Bethany Smith

BrainStorm to Present at Two Scientific Conferences in May – Yahoo Finance

May 1st, 2017

HACKENSACK, N.J. and PETACH TIKVAH, Israel, May 1, 2017 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (BCLI), a leading developer of adult stem cell technologies for neurodegenerative diseases, announced today that the Company will present data from its Phase 2 clinical study of NurOwn in amyotrophic lateral sclerosis (ALS) at the International Society for Cellular Therapy (ISCT) annual conference in London, England, and the World Advanced Therapy and Regenerative Medicine Congress in London, England.

International Society for Cellular Therapy Annual Conference

Date:

Thursday, May 4

Time:

3:30pm - 5:00pm CET

Location:

ExCeL London, London, England

Title:

Safety and Efficacy of Transplantation of NurOwn (Autologous Mesenchymal Stromal Cells Secreting Neurotrophic Factors) in Patients with ALS: a Phase 2 Randomized Double Blind Placebo Controlled Trial

Presenter:

Dr. Yael Gothelf, Chief Regulatory and Scientific Officer, BrainStorm Cell Therapeutics

Date:

Thursday, May 4

Time:

5:00pm - 6.30pm CET

Location:

ExCeL London, London, England

Title:

Poster presentation titled: In vivo modulation of neurotrophic and inflammatory factors in the CSF of ALS patients treated with NurOwn (MSC NTF cells)

Presenter:

Dr. Yael Gothelf, Chief Regulatory and Scientific Officer, BrainStorm Cell Therapeutics

World Advanced Therapies & Regenerative Medicine Congress 2017

Date:

Thursday, May 18

Time:

2:40pm CET

Location:

Business Design Centre, London

Title:

Brainstorm's NurOwn Treatment for Neurodegenerative Diseases

Presenter:

Chaim Lebovits, Chief Executive Officer, BrainStorm Cell Therapeutics

About the International Society for Cellular TherapyEstablished in 1992, the International Society for Cellular Therapy (ISCT) is a global society of clinicians, researchers, regulators, technologists and industry partners with a shared vision to translate cellular therapy into safe and effective therapies to improve patients' lives worldwide. ISCT is the global leader focused on pre-clinical and translational aspects of developing cell-based therapeutics, thereby advancing scientific research into innovative treatments for patients. ISCT offers a unique collaborative environment that addresses three key areas of translation: Academia, Regulatory and Commercialization. Through strong relationships with global regulatory agencies, academic institutions and industry partners, ISCT drives the advancement of research into standard of care. Comprised of over 1300 cell therapy experts across five geographic regions and representation from over 50 countries, ISCT members are part of a global community of peers, thought leaders and organizations invested in cell therapy translation. For more information about the society, key initiatives and upcoming meetings, please visit: http://www.celltherapysociety.org.

About the World Advanced Therapies & Regenerative Medicine Congress12 years ago when the World Stem Cells Congress was launched, the stem cells sector was one of scientific interest. Focusing on the challenges of how to transform these little precursor cells eventually into new tissues and organs. The first stem cells conference was relatively small with only 80 people attending the first event, but we knew we were on the verge of something huge and exciting. In May 2017 the newly named World Advanced Therapies & Regenerative Medicine Congress, will bring together 800+ attendees and explore the rapidly developing world of ATMPs (Advanced Therapy Medicinal Products). From process development to clinical translation this congress will bring you the most exciting case studies and new data. Experts in every area will help you tackle the process and regulatory hurdles of developing these new therapeutic formats all the way through manufacture and into the clinic.

About BrainStorm Cell Therapeutics Inc.BrainStorm Cell Therapeutics Inc. is a biotechnology company engaged in the development of first-of-its-kind adult mesenchymal stem cell therapies derived from autologous bone marrow cells for the treatment of neurodegenerative diseases. The Company holds the rights to develop and commercialize its NurOwn technology through an exclusive, worldwide licensing agreement with Ramot, the technology transfer company of Tel Aviv University. NurOwn has been administered to approximately 75 patients with ALS in clinical trials conducted in the United States and Israel. In a randomized, double-blind, placebo-controlled clinical trial conducted in the U. S., a clinically meaningful benefit was demonstrated by higher response to NurOwn compared with placebo. For more information, visit the company's website at http://www.brainstorm-cell.com.

SMART cells to fight arthritis – Cosmos

May 1st, 2017

An artist's impression of a reprogrammed stem cell.

Ella Marushchenko

In a curious confluence of the information technology industrys favourite word and scientists weakness for punning acronyms, researchers in St Louis, Missouri, in the US, have created what have been dubbed SMART cells.

SMART, in this case, stands for Stem cells Modified for Autonomous Regenerative Therapy, and their creation by a team based jointly at the Washington University School of Medicine and Shriners Hospital for Children promises a novel treatment for arthritis and other chronic conditions.

The team, led by Washington Universitys Farshid Guilak, reasoned that much of the pain and discomfort endured by arthritis suffers arises from inflammation caused by damaged cartilage. Reducing that inflammation, therefore, is an important therapeutic outcome.

To test this the team used mice. First, they harvested skin cells from tails, then turned them into stem cells. Next, using CRISPR gene-editing technology they excised a gene associated with inducing inflammation and replaced it with one that dampens it.

The resulting cells were then induced to grow into cartilage cells in cultures. The tissue thus produced was found to be free of inflammation.

In a clever move perhaps making the stem cells doubly smart Guilak and his colleagues further modified the stem cells so that they would light up when experiencing inflammation, making them easy to spot.

The research is published in in the journal Stem Cell Reports, and includes the news that research has now commenced using live mice.

Should the SMART cells eventually be found to be a viable avenue for human treatment, the results promise to be both more effective and better focused than existing arthritis drugs.

Pharmacological approaches to arthritis treatment mainly target the inflammation-promoting molecule called tumor necrosis factor alpha. The problem, however, is that they all do so on a system-wide basis, weakening the immune system and making patients more liable to infection.

We want to use our gene-editing technology as a way to deliver targeted therapy in response to localised inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body, says Guilak.

Study co-author Jonathan Brunger says the most pleasing aspect of the teams CRISPR-based approach is that it effectively highjacks the inflammatory pathway and turns it into a protective mechanism.

The ability to build living tissues from smart stem cells that precisely respond to their environment opens up exciting possibilities for investigation in regenerative medicine, he adds.

Read more from the original source:
SMART cells to fight arthritis - Cosmos

Recommendation and review posted by simmons

CRISPR Technology Scientists on Their Gene Editing Tool – TIME

May 1st, 2017

BY ALICE PARK

Dr. Carl Junes lab at the University of Pennsylvania looks like any other biology research hub. There are tidy rows of black-topped workbenches flanked by shelves bearing boxes of pipettes and test tubes. Theres ad hoc signage marking the different workstations. And there are postdocs buzzing around, calibrating scales, checking incubators and smearing solutions and samples onto small glass slides.

Appearances aside, what June is attempting to do here, on the eighth floor of the glass-encased Smilow Center for Translational Research in Philadelphia, is anything but ordinary. Hes built a career trying to improve the odds for people with intractable end-stage disease, and now, in the universitys brand-new cell-processing lab, hes preparing to launch his most ambitious study yet: hes going to try to treat 18 people with stubborn cancers, and hes going to do it using CRISPR, the most controversial new tool in medicine.

Developed just four short years ago by two groupsJennifer Doudna, a molecular and cell biologist at the University of California, Berkeley, together with Emmanuelle Charpentier, now at the Max Planck Institute in Berlin; and Feng Zhang, a biomedical engineer at the Broad Institute of Harvard and MITCRISPR allows scientists to easily and inexpensively find and alter virtually any piece of DNA in any species. In 2016 alone it was used to edit the genes of vegetables, sheep, mosquitoes and all kinds of cell samples in labs. Now, even as some scientists call for patience and extreme caution, theres a worldwide race to push the limits of CRISPRs capabilities.

Junes ultimate goal is to test CRISPRs greatest potential: its ability to treat diseases in humans. Before we were kind of flying in the dark when we were making gene changes, he says of earlier attempts at genetic tinkering. With CRISPR, I came to the conclusion that this technology needs to be tested in humans. The trial, which will start treating patients in a few months, is the first to use this powerful technique in this way. It represents the most extensive manipulation of the human genome ever attempted.

Soon, Junes 18 trial patients will become the first people in the world to be treated with CRISPRd cellsin this case, cells genetically edited to fight cancer. Like many people with cancer, the patients have run out of options. So, building on work by Doudna, Charpentier and Zhang, Junes team will extract their T cells, a kind of immune cell, and use CRISPR to alter three genes in those cells, essentially transforming them into superfighters. The patients will then be reinfused with the cancer-fighting T cells to see if they do what theyre supposed to do: seek and destroy cancerous tumors.

A lot of hope hangs on the outcome of the trial, but whether it succeeds or fails, it will provide scientists with critical information about what can go right and wrong when they try to rewrite the genetic code in humans. The hope is that studies like Junes will bear out CRISPRs therapeutic potential, leading to the development of radical new therapies not just for people with the cancers being studied but for all of them, as well as for genetic diseases such as sickle-cell anemia and cystic fibrosis, and chronic conditions like Type 2 diabetes and Alzheimers. It may sound far-fetched, but studies like this one are an enormous first step in that direction.

Using CRISPR on humans is still hugely controversial, in part because its so easy. The fact that it allows scientists to efficiently edit any genefor some cancers, but also potentially for a predisposition for red hair, for being overweight, for being good at mathworries ethicists because of what could happen if it gets into the wrong hands. As of now, the National Institutes of Health (NIH), by far the worlds largest sponsor of scientific research, will not fund studies using CRISPR on human embryos. And any new way of altering genes in human cells must get ethics and safety approval by the NIH, regardless of who is paying for it. (The NIH also opposes the use of CRISPR on so-called germ-line cellsthose in an egg, sperm or embryosince any such changes would be permanent and heritable.)

To fund his study, June was able to attract support from Sean Parker, the former Facebook executive and Silicon Valley entrepreneur behind Napster. Parker recently founded the $250 million Parker Institute for Cancer Immunotherapy, a collaboration among six major cancer centers, and Junes study is its first ambitious undertaking. We need to take big, ambitious bets to advance cancer treatment, says Parker. Were trying to lead the way in doing more aggressive, cutting-edge stuff that couldnt get funded if we werent around.

Thats not to say Junes study will necessarily cure these cancers. Either its back to the drawing board, he says, or everyone goes forward and studies a wide variety of other diseases that could potentially be fixed. In reality, both things are probably true.

Even if Junes study doesnt work as he hopes, experts still agree it will be a matter of monthsnot yearsbefore other privately funded human studies get launched in the U.S. and abroad. An ongoing patent battle over who owns the lucrative technology hasnt stopped investors from pouring millions into CRISPR companies. So simple and inexpensive is the technique, and so frenzied is the medical community about its potential, that it would be foolish to bet on anything else. With a technology like CRISPR, says Doudna, youve lit a fire.

A Year of Progress CRISPRs journey from lab bench to cancer treatment may seem quick. After all, as recently as a couple of years ago only a minuscule number of people even knew what clustered regularly interspaced short palindromic repeatsthats longhand for CRISPRwas. But the technology is at least hundreds of millions of years old. It was bacteria that originally used CRISPR, as a survival mechanism to fend off infection by viruses. The ultimate freeloaders, viruses never bothered developing their own reproductive system, preferring instead to insert their genetic material into that of other cellsincluding bacteria. Bacteria fought back, holding on to snippets of a virus genes when they were infected. The bacteria would then surround these viral DNA fragments with a genetic sequence that effectively cut them out altogether.

Bacteria have been performing that clever evolutionary stunt for millennia, but it wasnt until the early 2000s that food scientists at a Danish yogurt company realized just how clever the bacterial system was when they noticed that their cultures were turning too sour. They discovered that the cultures were CRISPRing invaders, altering the taste considerably. It made for bad dairy, but the scientific discovery was immediately recognized as a big one.

About a decade later, in 2012, Doudna and Charpentier tweaked the system to make it more standardized and user-friendly, and showed that not just bacterial DNA but any piece of DNA has this ability. That was a game changer. Scientists have been mucking with plant, animal and human DNA since its structure was first discovered by James Watson and Francis Crick in 1953. But altering genes, especially in deliberate, directed ways, has never been easy. The idea of gene correction is not new at all, says June. But before CRISPR it just never worked well enough so that people could do it routinely.

Within months of Doudnas and Charpentiers discovery, Zhang showed that the technique worked to cut human DNA at specified places. With that, genetics changed overnight. Now scientists had a tool allowing them, at least in theory, to wield unprecedented control over any genome, making it possible to delete bits of DNA, add snippets of genetic material and even insert entirely new pieces of code.

Now, that theoretical potential took shape in a remarkable array of real-world applications. CRISPR produced the first mushroom that doesnt brown, the first dogs with DNA-boosted cells giving them a comic-book-like musculature, and a slew of nutritionally superior crops that are already on their way to market. There are even efforts to use CRISPRd mosquitoes to fight Zika and malaria.

On the human side, progress has been even more dramatic. In a lab, scientists have successfully snipped out HIV from infected human cells and demonstrated that the process works in infected mice and rats as well. Theyre making headway in correcting the genetic defect behind sickle-cell anemia, which stands to actually cure the disease. Theyre making equally promising progress in treating rare forms of genetic blindness and muscular dystrophy. And in perhaps the most controversial application of CRISPR to date, in 2016 the U.K. approved the first use of the technology in healthy human embryos for research.

At the Francis Crick Institute in London, developmental biologist Kathy Niakan is using CRISPR to try to understand one of the more enduring mysteries of human development: what goes wrong at the earliest stages, causing an embryo to die and a pregnancy to fail. To be clear, Niakan will not attempt to implant the embryos in a human; her research is experimental, and the embryos are destroyed seven days after the studies begin.

Like Niakan, June is looking for answers to one of human biologys more vexing problems: why the immune system, designed to fight disease, is nearly useless against cancer. Its an issue thats kept him up at night since 2001, when his wife, not responding to the many treatments she tried, died of ovarian cancer.

This trial is about two things: safety and feasibility, he says. Its about testing whether its even possible to successfully edit these immune cells to make them doin human bodies, not a petri dishwhat he wants them to do. Either way, the study will yield critical information, paving the way for eventual new treatment options that are more targeted, less brutal and far smarter against tumors than systemwide chemotherapy will ever be.

As much as has been done in 2016, this is only the beginning of a kind of medicine that stands to effectively change the course of human history. CRISPR is an empowering technology with broad applications in both basic science and clinical medicine, says Dr. Francis Collins, director of the NIH. It will allow us to tackle problems that for a long time we probably felt were out of our reach.

The Hurdles Ahead Because its so easy to use, Zhang, along with the other CRISPR pioneers, says careful thought should be given to where and how it gets employed. For the most part I dont think we are getting ahead of ourselves with the CRISPR applications, he says. What we need to do is really engage the public, to make sure people understand what are the really exciting potential applications and what are the immediate limitations of the technology, so we really are applying it and supporting it in the right way.

Regulatory scrutiny is a given with CRISPR, and any new tool for rewriting human DNA requires federal approval. For the current Penn trial, June got the green light from the NIH Recombinant DNA Advisory Committee, established in the 1980s to assess the safety of any first-in-humans gene-therapy trials. While there are still dangers involved in any kind of gene therapythe changes may happen in unexpected places, for example, or the edits may have unanticipated side effectsscientists have learned more about the best way to make the genetic changes, and how to deliver them more safely. So far, animal studies show CRISPR provides enough control that unexpected negative effects are rareat least so far.

The role of regulatory oversight is less clear when the technique is used to alter food crops. Even before Junes patients get infused with CRISPRd T cells, farmers in Argentina and Minnesota will plant the worlds first gene-edited crops for market. CRISPR provides an unparalleled ability to insert almost any trait into plantsdrought or pest resistance, more of this vitamin or less of that nutritional villain du jour. Dupont, for instance, is putting the finishing touches on its first drought-resistant corn, and biotech company Calyxt has created a potato that doesnt produce cancerous compounds when fried; its also planting its first crop of soy plants modified to produce higher amounts of healthy oleic-acid fats.

These edits involve deleting or amping up existing genesnot adding new ones from other speciesand the U.S. Department of Agriculture has said this kind of gene-edited food crop is not significantly different from unaltered crops and therefore does not need to be regulated differently.

In the coming months, the National Academy of Sciences is expected to issue guidelines that might address some of the challenges posed by CRISPR, focusing on how and when to proceed with developing new disease treatments. The report is expected to launch much-needed discussion in the scientific community and among the public as well. Whether more regulation will eventually be required likely depends on how far scientists push the limits of their editingand how comfortable consumers and advocacy groups are with those studies.

As CRISPR goes mainstream in medicine and agriculture, profound moral and ethical questions will arise. Few would argue against using CRISPR to treat terminal cancer patients, but what about treating chronic diseases? Or disabilities? If sickle-cell anemia can be corrected with CRISPR, should obesity, which drives so many life-threatening illnesses? Who decides where that line ought to be drawn?

Questions like these weigh heavily on June and all of CRISPRs pioneering scientists. Having this technology enables humans to alter human evolution, says Doudna. Thinking about all the different ways it can be employed, both for good and potentially not for very good, I felt it would be irresponsible as someone involved in the earliest stages of the technology not to get out and talk about it.

Last year, Doudna invited other leaders in genetics to a summit to address the immediate concerns about applying CRISPR to human genes. The group agreed to a voluntary temporary moratorium on using CRISPR to edit the genes of human embryos that would be inserted into a woman and brought to term, since the full array of CRISPRs consequences isnt known yet. (Any current research using human embryos, including Niakans, is lab-only.)

For researchers like June and Niakan, Doudna and Zhang, and others, proceeding carefully with CRISPR is the only way forward. But proceed they will. The sooner more answers emerge, the sooner CRISPR can mature and begin to deliver on its promise. There are thousands of applications for CRISPR, says June. The sky is the limit. But we have to be careful.

Read this article:

CRISPR Technology Scientists on Their Gene Editing Tool - TIME

Recommendation and review posted by simmons

Cas9 – Wikipedia

May 1st, 2017

Cas9 (CRISPR associated protein 9) is an RNA-guided DNA endonuclease associated with the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) type II adaptive immunity system in Streptococcus pyogenes, among other bacteria. S. pyogenes utilizes Cas9 to interrogate and cleave foreign DNA,[1] such as invading bacteriophage DNA or plasmid DNA.[2] Cas9 performs this interrogation by unwinding foreign DNA and checking whether it is complementary to the 20 basepair spacer region of the guide RNA. If the DNA substrate is complementary to the guide RNA, Cas9 cleaves the invading DNA. In this sense, the CRISPR-Cas9 mechanism has a number of parallels with the RNA interference (RNAi) mechanism in eukaryotes. Native Cas9 assists in all three CRISPR steps: it participates in adaptation, participates in crRNA processing and it cleaves the target DNA assisted by crRNA and an additional RNA called tracrRNA. Native Cas9 requires a guide RNA composed of two disparate RNAs that associate to make the guide - the CRISPR RNA (crRNA), and the trans-activating RNA (tracrRNA).,[3][4]

The Cas9 protein has been heavily utilized as a genome engineering tool to induce site-directed double strand breaks in DNA. These breaks can lead to gene inactivation or the introduction of heterologous genes through non-homologous end joining and homologous recombination respectively in many laboratory model organisms. Alongside zinc finger nucleases and TALEN proteins, Cas9 is becoming a prominent tool in the field of genome editing. Cas9 has gained traction in recent years because it can cleave nearly any sequence complementary to the guide RNA.[2] Because the target specificity of Cas9 stems from the guide RNA:DNA complementarity and not modifications to the protein itself (like TALENs and Zinc-fingers), engineering Cas9 to target new DNA is straightforward.[5][6] Versions of Cas9 that bind but do not cleave cognate DNA can be used to localize transcriptional activator or repressors to specific DNA sequences in order to control transcriptional activation and repression.[7][8] Cas9 targeting has been simplified through the engineering of a chimeric single guide RNA. Scientists have suggested that Cas9-based gene drives may be capable of editing the genomes of entire populations of organisms.[9] In 2015, scientists in China used Cas9 to modify the genome of human embryos for the first time.[10]

To survive in a variety of challenging, inhospitable habitats that are filled with bacteriophage, bacteria have evolved methods to evade and fend off predatory viruses. This includes the recently appreciated CRISPR system. CRISPR loci are composed of short, palindromic repeats that occur at regular intervals composed of alternate CRISPR repeats and variable CRISPR spacers. These CRISPR loci are usually accompanied by adjacent CRISPR-associated (cas) genes. In 2005, it was discovered by three separate groups that the spacer regions were homologous to foreign DNA elements, including plasmids and viruses. These reports provided the first biological evidence that CRISPRs might function as an immune system.

CRISPR-Cas systems are divided into two classes and many subtypes, based on their genetic content and structural differences. However, the core defining features of all CRISPR-Cas systems are the cas genes and their proteins: cas1 and cas2 are universal while cas3, cas9, and cas10 are signature genes specific subtypes.

The CRISPR-Cas defense can be described in three stages:

The three stages of the CRISPR-Cas adaptive immune system, based on the CRISPR-Cas system in Streptococcus thermophilus.

Stage 1: CRISPR spacer integration. Protospacers and protospacer-associated motifs (shown in red) are acquired at the leader end of a CRISPR array in the host DNA. The CRISPR array is composed of spacer sequences (shown in colored boxes) flanked by repeats (black diamonds). This process requires Cas1 and Cas2 (and Cas9 in type II[1]), which are encoded in the cas locus, which are usually located near the CRISPR array.

Stage 2: CRISPR expression. Pre-crRNA is transcribed starting at the leader region by the host RNA polymerase and then cleaved by Cas proteins into smaller crRNAs containing a single spacer and a partial repeat (shown as hairpin structure with colored spacers).

Stage 3: CRISPR interference. crRNA with a spacer that has strong complementarity to the incoming foreign DNA begins a cleavage event (depicted with scissors), which requires Cas proteins. DNA cleavage interferes with viral replication and provides immunity to the host. The interference stage can be functionally and temporarily distinct from CRISPR acquisition and expression (depicted by white line dividing the cell) [4].

Cas9 features a bi-lobed architecture with the guide RNA nestled between the alpha-helical lobe (blue) and the nuclease lobe (cyan, orange and gray). These two lobes are connected through a single bridge helix. There are two nuclease domains located in the multi-domain nuclease lobe, the RuvC (gray) which cleaves the non-target DNA strand, and the HNH nuclease domain (cyan) that cleaves the target strand of DNA. Interestingly, the RuvC domain is encoded by sequentially disparate sites that interact in the tertiary structure to form the RuvC cleavage domain.

A key feature of the target DNA is that it must contain a protospacer adjacent motif (PAM) consisting of the three-nucleotide sequence- NGG. This PAM is recognized by the PAM-interacting domain (PI domain, orange) located near the C-terminal end of Cas9. Cas9 undergoes distinct conformational changes between the apo, guide RNA bound, and guide RNA:DNA bound states, which are detailed below. PAM is recognized by Arg 1333 and Arg 1335 in the major groove by a - hairpin, where they bind to dG2 and dG3 of PAM.[14]

Cas9 recognizes the stem-loop architecture inherent in the CRISPR locus, which mediates the maturation of crRNA-tracrRNA ribonucleoprotein complex.[15] Cas9 in complex with CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) further recognizes and degrades the target dsDNA.[16] In the co-crystal structure shown here, the crRNA-tracrRNA complex is replaced by a chimeric single-guide RNA (sgRNA, in red) which has been proved to have the same function as the natural RNA complex.[17] The sgRNA base paired with target ssDNA is anchored by Cas9 as a T-shaped architecture. This crystal structure of the DNA-bound Cas9 enzyme reveals distinct conformational changes in the alpha-helical lobe with respect to the nuclease lobe, as well as the location on the HNH domain. protein consists of a recognition lobe (REC) and a nuclease lobe (NUC). It should be noted that all regions except the HNH form tight interactions with each other and sgRNA-ssDNA complex, while the HNH domain forms few contacts with the rest of the protein. In another conformation of Cas9 complex observed in the crystal, the HNH domain is not visible. These structures suggest the conformational flexibility of HNH domain.

Several crystal structures have been published, including:

In sgRNA-Cas9 complex, based on the crystal structure, REC1, BH and PI domains have important contacts with backbone or bases in both repeat and spacer region.[23][24] Several Cas9 mutants including REC1 or REC2 domains deletion and residues mutations in BH have been tested. REC1 and BH related mutants show lower or none activity compared with wild type, which indicate these two domains are crucial for the sgRNA recognition at repeat sequence and stabilization of the whole complex. Although the interactions between spacer sequence and Cas9 as well as PI domain and repeat region need further studies, the co-crystal demonstrates clear interface between Cas9 and sgRNA. Indeed, the recent crystal structure of Cas9 bound to single-guide RNA reveals that the 10-nucleotide RNA seed sequence is preordered in an A-form conformation for target DNA recognition. In addition to the pre-ordered seed sequences, comparison of the Cas9-sgRNA complex with the target DNA-bound structure (PDB 4UN3) reveals that the PAM-interacting sites (R1333 and R1335) responsible for 5-NGG-3 PAM recognition are pre-positioned prior to binding target DNA. Together, these structural observations show that the spacer region of sgRNA, especially the seed region, is essential for triggering Cas9 to form a DNA recognition-competent structure that is ready to engage double-stranded DNA target sequences.[21]

Previous sequence analysis and biochemical studies have suggested Cas9 contain RNase H and HNH endonuclease homologous domains which are responsible for cleavages of two target DNA strands, respectively. These results are finally proved in the structure. Although the low sequence similarity, the sequence similar to RNase H has a RuvC fold (one member of RNase H family) and the HNH region folds as T4 Endo VII (one member of HNH endonuclease family). Previous works on Cas9 have demonstrated that HNH domain is responsible for complementary sequence cleavage of target DNA and RuvC is responsible for the non-complementary sequence (Westra, et al. 2012; Wiedenheft, et al. 2014).

Due to the unique ability of Cas9 to bind to essentially any complement sequence in any genome, researchers wanted to use this enzyme to repress transcription of various genomic loci. To accomplish this, the two crucial catalytic residues of the RuvC and HNH domain can be mutated to alanine abolishing all endonuclease activity of Cas9. The resulting protein coined dead Cas9 or dCas9 for short, can still tightly bind to dsDNA. This catalytically inactive Cas9 variant has been used for both mechanistic studies into Cas9 DNA interrogative binding and as a general programmable DNA binding RNA-Protein complex.

The interaction of dCas9 with target dsDNA is so tight that high molarity urea protein denaturant can not fully dissociate the dCas9 RNA-protein complex from dsDNA target.[25] dCas9 has been targeted with engineered single guide RNAs to transcription initiation sites of any loci where dCas9 can compete with RNA polymerase at promoters to halt transcription.[26] Also, dCas9 can be targeted to the coding region of loci such that inhibition of RNA Polymerase occurs during the elongation phase of transcription.[26] In Eukaryotes, silencing of gene expression can be extented by targeting dCas9 to enhancer sequences, where dCas9 can block assembly of transcription factors leading to silencing of specific gene expression.[8] Moreover, the guide RNAs provided to dCas9 can be designed to include specific mismatches to its complementary cognate sequence that will quantitatively weaken the interaction of dCas9 for its programmed cognate sequence allowing a researcher to tune the extent of gene silencing applied to a gene of interest.[26] This technology is similar in principle to RNAi such that gene expression is being modulated at the RNA level. However, the dCas9 approach has gained much traction as there exist less off-target effects and in general larger and more reproducible silencing effects through the use of dCas9 compared to RNAi screens.[27] Furthermore, because the dCas9 approach to gene silencing can be quantitatively controlled, a researcher can now precisely control the extent to which a gene of interest is repressed allowing more questions about gene regulation and gene stoichiometry to be answered.

Beyond direct binding of dCas9 to transcriptionally sensitive positions of loci, dCas9 can be fused to a variety of modulatory protein domains to carry out a myriad of functions. Recently, dCas9 has been fused to chromatin remodeling proteins(HDACs/HATs) to reorganize the chromatin structure around various loci.[26] This is an important in targeting various eukaryotic genes of interest as heterochromatin structures hinder Cas9 binding. Furthermore, because Cas9 can react to heterochromatin, it is theorized that this enzyme can be further applied to studying the chromatin structure of various loci.[26] Additionally, dCas9 has been employed in genome wide screens of gene repression. By employing large libraries of guide RNAs capable of targeting thousands of genes, genome wide genetic screens using dCas9 have been conducted.[28]

Another method for silencing transcription with Cas9 is to directly cleave mRNA products with the catalytically active Cas9 enzyme.[29] This approach is made possible by hybridizing ssDNA with a PAM complement sequence to ssRNA allowing for a dsDNA-RNA PAM site for Cas9 binding. This technology makes available the ability to isolate endogenous RNA transcripts in cells without the need to induce chemical modifications to RNA or RNA tagging methods.

In contrast to silencing genes, dCas9 can also be used to activate genes when fused to transcription activating factors.[26] These factors include subunits of bacterial RNA Polymerase II and traditional transcription factors in Eukaryotes. Recently, genome wide screens of transcription activation have also been accomplished using dCas9 fusions named CRISPRa for activation.[28]

Original post:

Cas9 - Wikipedia

Recommendation and review posted by sam

CRISPR | Broad Institute

May 1st, 2017

The CRISPR system

Like zinc fingers and TALEs, CRISPR systems are natural products. However, CRISPR-Cas differs from zinc fingers and TALEs in one crucial aspect that makes it superior for genome editing applications: whereas zinc fingers and TALEs bind to DNA through a direct protein-DNA interaction, requiring the protein to be redesigned for each new target DNA site, CRISPR-Cas achieves target specificity through a small RNA that can easily be swapped for other RNAs targeting new sites.

In nature, CRISPR-Cas systems help bacteria defend against attacking viruses (known as bacteriophage or just phage). They consist of two components, the CRISPR (clustered, regularly interspaced palindromic repeats) array and Cas (CRISPR-associated) proteins. CRISPR sequences bookend short stretches of DNA that bacteria have copied from invading phages, preserving a memory of the viruses that have attacked them in the past. These sequences are then transcribed into short RNAs that guide Cas proteins to matching viral sequences. The Cas proteins destroy the matching viral DNA by cutting it. There are a number of different types of CRISPR-Cas systems in nature, which vary in their components; the CRISPR-Cas9 system uses just a single protein, Cas9, to find and destroy target DNA. In 2015, Zhang and colleagues successfully harnessed a second system, called CRISPR-Cpf1, which has the potential for even simpler and more precise genome engineering.

In early 2011, Feng Zhang was just starting his own research group at the Broad Institute and MIT, where he is an investigator at the McGovern Institute for Brain Research and a faculty member in the departments of Brain and Cognitive Sciences and Biological Engineering.After learning about existing CRISPR researchat a scientific meeting at the Broad, he quickly realized that the system, with a single RNA-guided protein, could be a game changer in genome editing technology. He was already working on DNA targeting methods, having helped to develop the TALE system as a Junior Fellow at Harvard. This system could target and activate genes in mammalian genomes.

Zhang and his team focused on harnessing CRISPR-Cas9 for use in human cells. In January 2013, he reported the first successful demonstration of Cas9-based genome editing in human cells in what has become the most-cited CRISPR paper (Cong et al., Science, 2013). Researchers from George Churchs lab at Harvard University reported similar findings in the same issue of Science (Mali et al., Science, 2013). The Zhang and Church papers showed that Cas9 could be targeted to a specific location in the human genome and cut the DNA there. The cut DNA was then repaired by inserting a new stretch of DNA, supplied by the researchers, essentially achieving find and replace functionality in the human genome.

In September, 2015, Zhang and partners described a different system, Cpf1, which appears to have significant implications for research and therapeutics.The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues.

The CRISPR toolbox is continuing to expand rapidly, opening new avenues for biomedical research. Since the first publications in early 2013, the Zhang lab and other researchers have engineered a number of improvements to the system. For example, Cas9 has been modified so that instead of cutting the target DNA, it can turn gene expression on by recruiting transcriptional activators to its genomic location (Konermann, et al., Nature, 2014).

At the Broad Institute, the system has also been used for genome-wide screens to identify genes involved in resistance to cancer drugs and dissect immune regulatory networks. CRISPR has been used to rapidly create mouse models of cancer that arise from multiple gene alterations (Platt et al., Cell, 2014). In 2015, Zhang and his team reported success with Cas9 derived from a different bacterium, Staphylococcus aureus (SaCas9). SaCas9 is smaller than the original Cas9, which has advantages for gene therapy (Ran et al., Nature, 2015).

The Zhang lab has trained thousands of researchers in the use of CRISPR-Cas9 genome editing technology through direct education and by sharing more than 37,000 CRISPR-Cas9 components with academic laboratories around the world to help accelerate global research that will benefit human health. In September 2015, the Zhang lab also began to share Cpf1 components.

Users can obtain guide sequences for knock-outs and transcriptional activation as well as information about genome-wide libraries for CRISPR-based screening. To learn more, visit the Zhang Lab CRISPR Resources at http://www.genome-engineering.org/.

Read this article:

CRISPR | Broad Institute

Recommendation and review posted by simmons

Questions and Answers about CRISPR | Broad Institute

May 1st, 2017

Q: What is CRISPR?

A: CRISPR (pronounced crisper) stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system which forms the basis for the popular CRISPR-Cas9 genome editing technology. In the field of genome engineering, the term CRISPR is often used loosely to refer to the entire CRISPR-Cas9 system, which can be programmed to target specific stretches of genetic code and to edit DNA at precise locations. These tools allow researchers to permanently modify genes in living cells and organisms and, in the future, may make it possible to correct mutations at precise locations in the human genome to treat genetic causes of disease. In September 2015, the Zhang lab demonstrated successful harnessing of a different CRISPR system for genome editing, called CRISPR-Cpf1, which has the potential for even simpler and more precise genome engineering.

Q: Where do CRISPRs come from?

A: CRISPRs were first discovered in archaea (and later in bacteria), by Francisco Mojica, a scientists at the University of Alicante in Spain. He proposed that CRISPRs serve as part of the bacterial immune system, defending against invading viruses. They consist of repeating sequences of genetic code, interrupted by spacer sequences remnants of genetic code from past invaders. The system serves as a genetic memory that helps the cell detect and destroy invaders (called bacteriophage) when they return. Mojicas theory was experimentally demonstrated in 2007 by a team of scientists led by Philippe Horvath.

In January 2013, Feng Zhang at the Broad Institute and MIT published the first method to engineer CRISPR to edit the genome in mouse and human cells.

Q: How does the system work?

A: CRISPR spacer sequences are transcribed into short RNA sequences (CRISPR RNAs or crRNA) capable of guiding the system to matching sequences of DNA. When the target DNA is found, Cas9 one of the enzymes produced by the CRISPR system binds to the DNA and cuts it, shutting the targeted gene off. Using modified versions of Cas9, researchers can activate gene expression instead of cutting the DNA. These techniques allow researchers to study the genes function.

Research also suggests that CRISPR-Cas9 can be used to target and modify typos in the three-billion-letter sequence of the human genome in an effort to treat genetic disease.

Q: How does CRISPR-Cas9 compare to other genome editing tools?

A: CRISPR-Cas9 is proving to be an efficient and customizable alternative to other existing genome editing tools. Since the CRISPR-Cas9 system itself is capable of cutting DNA strands, CRISPRs do not need to be paired with separate cleaving enzymes as other tools do. They can also easily be matched with tailor-made guide RNA (gRNA) sequences designed to lead them to their DNA targets. Tens of thousands of such gRNA sequences have already been created and are available to the research community. CRISPR-Cas9 can also be used to target multiple genes simultaneously, which is another advantage that sets it apart from other gene-editing tools.

CRISPR-Cpf1differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics.

First: In its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues.

Second, and perhaps most significantly: Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving blunt ends that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately.

Third: Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur.

Fourth: the Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting some genomes, such as in the malaria parasite as well as in humans.

Here is the original post:

Questions and Answers about CRISPR | Broad Institute

Recommendation and review posted by simmons

CRISPR Genome Engineering Resources | learn, share, and discuss

May 1st, 2017

Mar. 2015: We are excited to announceGenome Engineering 3.0,a 2-day practical workshop designed to help you use CRISPR-Cas9 system to perform all different types of genome engineering tasks more effectively in your own work.It will be held from May 8-9, 2015 at the Broad Institute (map) in Cambridge, MA, USA.The workshop is open to all and free. For more details, please visit our workshop website, and if you are ready to sign up, you can register here.

Feb. 2014: Collaboration with Osamu Nureki and Hiroshi Nishimasuat University of Tokyoreveals crystal structure of Cas9 in complex with guide RNA and target DNA.

Dec. 2013: New Genome-scale CRISPR Knock-out (GeCKO) functional genomics screening study inShalem* and Sanjana* et al., Science, 2013and companion website.

July 2013: Based on the specificity analysis performed in Hsu et al., Nature Biotechnology 2013, we have released the CRISPR Design Tool. This tool allows users to search for high specificity SpCas9 target sites within DNA sequences of interest.

Apr. 2012: Have a question or need help with trouble shooting? Please visit our newly updated FAQs and Trouble Shooting Tips page.

Feb. 2013: For highest efficiency in genome targeting applications, please use our new chimeric RNA design with longer tracrRNA hybrid.In the earlier paper we useda shorter chimeric RNA design that is not optimal, now the new longer chimeric RNA design is most effective (better than crRNA:tracrRNA pair).This is verified by other published CRISPR paper as well.

Jan. 2013: Please feel free to post your questions to our CRISPR Discussion Forum.

Originally posted here:

CRISPR Genome Engineering Resources | learn, share, and discuss

Recommendation and review posted by Bethany Smith

CRISPR Gene Editing – CRISPR/Cas9 – Horizon Discovery

May 1st, 2017

CRISPR or CRISPR Cas 9 is commonly used to refer to a revolutionary genome editing technology that enables efficient and precise genomic modifications in a wide variety of organisms and tissues.

Definition: Clustered Regularly Interspaced Short Palindromic Repeat or CRISPR (pronounced 'crisper') was identified in a prokaryotic defence system. CRISPR are sections of genetic code containing short repetitions of base sequences followed by spacer DNA segments

Identified in archaea and bacteria, short nucleic acid sequences are captured from invading pathogens and integrated in the CRISPR loci amidst the repeats. Small RNAs, produced by transcription of these loci, can then guide a set of endonucleases to cleave the genomes of future invading pathogens, thereby disabling their attacks.

Definition: CRISPR Associated protein 9 (Cas 9) is an endonuclease used in an RNA-guided gene editing platform. It uses a synthetic guide RNA to introduce a double strand break at a specific location within a strand of DNA

Cas9 was the first of several restriction nucleases (or molecular scissors) discovered that enable CRISPR genome editing. The CRISPR-Cas 9 mechanism has since been adapted into a powerful tool that puts genome editing into the mainstream.

In the laboratory, Cas9 genome editing is achieved by transfecting a cell with the Cas9 protein along with a specially designed guide RNA (gRNA) that directs the cut through hybridization with its matching genomic sequence. When the cell repairs that break, errors can occur to generate a gene knockout or additional genetic modifications can be introduced. Our CRISPR technology is particularly good for the efficient generation of complete knockout of genes on multiple alleles.

Use of wild-type Cas 9 has been shown to lead to off-target cleavage, but a modified version introduces only single strand nicks to the DNA, which in pairs still stimulate the repair mechanisms while significantly decreasing the risk of off-target cutting.

Horizon has licensed gene editing IP from Harvard University, the Broad Institute and ERS Genomics with the goal of being able to ensure that we will be able to offer uninterrupted use of CRISPR technology to our customers. Our scientists have extensive knowledge of CRISPR technology including the benefits of using each Cas9 structure.

Other Gene Editing Systems

Genome editing can be achieved using the widely used S. Pyogenes (spCas9), and also utilising CRISPR-Cas 9 protocol for S. Aureus (scCas9), Cpf1, HiFi Cas9, Nickase Cas9, Nuclease Cas9, NgAgo gDNA and even synthetic spCas9 with alternative PAM sites.

Our genome editing knowledge also includes rAAV and ZFNs.

Continue your research with our CRISPR/Cas9 videos:

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315(5819): 1709-1712.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096): 816-821.

Read the original:

CRISPR Gene Editing - CRISPR/Cas9 - Horizon Discovery

Recommendation and review posted by simmons

The Creepy, Insane, and Undeniably Romantic World of Cryonics – VICE

May 1st, 2017

I'd expected to hear a lot of convincing arguments that would persuade me to sign up to have my body cryogenically frozen when I die, but proving that I'm more rational than Paris Hilton wasn't one of them.

"About ten years ago there was a rumor going around that she had signed up to have her body preserved, so my colleagues and I worried that perhaps Paris Hilton was more rational than us," says Anders Sandberg, a research fellow with the University of Oxford's Future of Humanity Institute. Sandberg is an expert on human "enhancement" who himself is signed up to be frozen one day.

On one level, of course, doing anything because Paris Hilton pressured you into it is a really bad idea, Sandberg admits. "But we humans are emotional beings, so the fact that some of our Oxford academic pride was wounded really did spurn us to bite the bullet."

As insane, or perhaps creepy, as it sounds, hundreds of people in the US are 'frozen,' stored in stainless steel chambers at a cozy -196C in liquid nitrogen. Their cases are checked daily while they're kept "in stasis," as cryonic believers call it, waiting until new medical technologies can cure or repair whatever ailed them, whether it be a heart attack, dementia, or perhaps even cancer. At the Alcor Life Extension Foundation in Scottsdale Arizona, 150 "patients" are frozen in time, and another 996 have signed up for the same fate.

The Cryonics Institute in Clinton township, Michigan holds a similar number150 humans, plus more than 100 pets. "Maybe the idea of reviving people who are cryogenically frozen sounds far-fetched, but in my field, you know that you can bring back the dead all the time," says Dennis Kowalski, a director at the Cyronics Institute who works as a paramedic by day. "I've been able to take a lot of what I learned from emergency medicine and integrate it into cryonics. You don't need to reinvent the wheel. Death is a process, and we simply slow that process down. I like to say that we provide the ambulance to the hospital of the future."

Moreover, Sandberg points out, there are thousandsif not millionsof people alive today who were once frozen sperm or egg cells, or frozen embryos. "In a sense, those people were cryonically frozen, and yet they are today alive," he says. Moving up in size, scientists demonstrated last year that embryonic rabbit kidneys could be frozen, thawed, and grown into full-sized and fully functional organs, capable of transplant into living animals.

In the wild, Canadian wood frogs annually freeze solid, thanks to special proteins in their blood that act as a natural antifreeze and prevent the formation of ice crystals that would cause cell damageso it is theoretically possible for an entire body to be kept below freezing temperature and later revived. Cryonisists have already been replicating this strategy for decades: All preserved bodies are not technically "frozen," because all the blood is drained out the moment they legally die, and slowly replaced with a biological antifreeze (along with a cocktail of more than a dozen different drugs) that perfuses into the body and prevents ice crystals from forming and damaging cells. Hence why a body that would be a toasty 32C can be kept at -196C potentially indefinitely. But sperm, eggs, kidneys, and frogs are one thing. What about that most human of organs, the brain? There's no point in being revived if your memories, knowledge, and personality don't come with you.

Read the full story at Tonic.

Originally posted here:
The Creepy, Insane, and Undeniably Romantic World of Cryonics - VICE

Recommendation and review posted by Bethany Smith

Fighting the common fate of humans: to better life and beat | Cosmos – Cosmos

May 1st, 2017

Can technology help us to beat death?

ANDRZEJ WOJCICKI/SCIENCE PHOTO LIBRARY/GETTY

The oldest surviving great work of literature tells the story of a Sumerian king, Gilgamesh, whose historical equivalent may have ruled the city of Uruk some time between 2800 and 2500 BC.

A hero of superhuman strength, Gilgamesh becomes instilled with existential dread after witnessing the death of his friend, and travels the Earth in search of a cure for mortality.

Twice the cure slips through his fingers and he learns the futility of fighting the common fate of man.

Transhumanism is the idea that we can transcend our biological limits, by merging with machines. The idea was popularised by the renowned technoprophet Ray Kurzweil (now a director of engineering at Google), who came to public attention in the 1990s with a string of astute predictions about technology.

In his 1990 book, The Age of Intelligent Machines (MIT Press), Kurzweil predicted that a computer would beat the worlds best chess player by the year 2000. It happened in 1997.

He also foresaw the explosive growth of the internet, along with the advent of wearable technology, drone warfare and the automated translation of language. Kurzweils most famous prediction is what he calls the singularity the emergence of an artificial super-intelligence, triggering runaway technological growth which he foresees happening somewhere around 2045.

In some sense, the merger of humans and machines has already begun. Bionic implants, such as the cochlear implant, use electrical impulses orchestrated by computer chips to communicate with the brain, and so restore lost senses.

At St Vincents Hospital and the University of Melbourne, my colleagues are developing other ways to tap into neuronal activity, thereby giving people natural control of a robotic hand.

These cases involve sending simple signals between a piece of hardware and the brain. To truly merge minds and machines, however, we need some way to send thoughts and memories.

In 2011, scientists at the University of Southern California in Los Angeles took the first step towards this when they implanted rats with a computer chip that worked as a kind of external hard drive for the brain.

First the rats learned a particular skill, pulling a sequence of levers to gain a reward. The silicon implant listened in as that new memory was encoded in the brains hippocampus region, and recorded the pattern of electrical signals it detected.

Next the rats were induced to forget the skill, by giving them a drug that impaired the hippocampus. The silicon implant then took over, firing a bunch of electrical signals to mimic the pattern it had recorded during training.

Amazingly, the rats remembered the skill the electrical signals from the chip were essentially replaying the memory, in a crude version of that scene in The Matrix where Keanu Reeves learns (downloads) kung-fu.

Again, the potential roadblock: the brain may be more different from a computer than people such as Kurzweil appreciate. As Nicolas Rougier, a computer scientist at Inria (the French Institute for Research in Computer Science and Automation), argues, the brain itself needs the complex sensory input of the body in order to function properly.

Separate the brain from that input and things start to go awry pretty quickly. Hence sensory deprivation is used as a form of torture. Even if artificial intelligence is achieved, that does not mean our brains will be able to integrate with it.

Whatever happens at the singularity (if it ever occurs), Kurzweil, now aged 68, wants to be around to see it. His Fantastic Voyage: Live Long Enough to Live Forever (Rodale Books, 2004) is a guidebook for extending life in the hope of seeing the longevity revolution. In it he details his dietary practices, and outlines some of the 200 supplements he takes daily.

Failing that, he has a plan B.

The central idea of cryonics is to preserve the body after death in the hope that, one day, future civilisations will have the ability (and the desire) to reanimate the dead.

Both Kurzweil and de Grey, along with about 1,500 others (including, apparently, Britney Spears), are signed up to be cryopreserved by Alcor Life Extension Foundation in Arizona.

Offhand, the idea seems crackpot. Even in daily experience, you know that freezing changes stuff: you can tell a strawberry thats been frozen. Taste, and especially texture, change unmistakably. The problem is that when the strawberry cells freeze, they fill with ice crystals. The ice rips them apart, essentially turning them to mush.

Thats why Alcor dont freeze you; they turn you to glass.

After you die, your body is drained of blood and replaced with a special cryogenic mixture of antifreeze and preservatives. When cooled, the liquid turns to a glassy state, but without forming dangerous crystals.

You are placed in a giant thermos flask of liquid nitrogen and cooled to -196, cold enough to effectively stop biological time. There you can stay without changing, for a year or a century, until science discovers the cure for whatever caused your demise.

People dont understand cryonics, says Alcor president Max More in a YouTube tour of his facility. They think its this strange thing we do to dead people, rather than understanding it really is an extension of emergency medicine.

The idea may not be as crackpot as it sounds. Similar cryopreservation techniques are already being used to preserve human embryos used in fertility treatments.

There are people walking around today who have been cryopreserved, More continues. They were just embryos at the time.

One proof of concept, of sorts, was reported by cryogenics expert Greg Fahy of 21st Century Medicine (a privately funded cryonics research lab) in 2009.

Fahys team removed a rabbit kidney, vitrified it, and reimplanted into the rabbit as its only working kidney. Amazingly, the rabbit survived, if only for nine days.

More recently, a new technique developed by Fahy enabled the perfect preservation of a rabbit brain though vitrification and storage at -196. After rewarming, advanced 3D imaging revealed that the rabbits connectome that is, the connections between neurons was undisturbed.

Unfortunately, the chemicals used for the new technique are toxic, but the work does raise the hope of some future method that may achieve the same degree of preservation with more friendly substances.

That said, preserving structure does not necessarily preserve function. Our thoughts and memories are not just coded in the physical connections between neurons, but also in the strength of those connections coded somehow in the folding of proteins.

Thats why the most remarkable cryonics work to date may be that performed at Alcor in 2015, when scientists managed to glassify a tiny worm for two weeks, and then return it to life with its memory intact.

Now, while the worm has only 302 neurons, you have more than 100 billion, and while the worm has 5,000 neuron-to-neuron connections you have at least 100 trillion. So theres some way to go, but theres certainly hope.

In Australia, a new not-for-profit, Southern Cryonics, is planning to open the first cryonics facility in the Southern Hemisphere.

Eventually, medicine will be able to keep people healthy indefinitely, Southern Cryonics spokesperson and secretary Matt Fisher tells me in a phonecall.

I want to see the other side of that transition. I want to live in a world where everyone can be healthy for as long as they want. And I want everyone I know and care about to have that opportunity as well.

To get Southern Cryonics off the ground, ten founding members have each put in A$50,000, entitling them to a cryonic preservation for themselves or a person of their choice. Given that the company is not-for-profit, Fisher has no financial incentive to campaign for it. He simply believes in it.

Id really like to see [cryonic preservation] become the most common choice for internment across Australia, he says.

Fisher admits there is no proof yet that cryopreservation works. The question is not about what is possible today, he says. Its about what may be possible in the future.

Cathal D. O'Connell, Centre Manager, BioFab3D (St Vincent's Hospital), University of Melbourne

This article was originally published on The Conversation and republished here with permission. Read the original article.

This piece is republished with permission from Millenials Strike Back, the 56th edition of Griffith Review. Selected pieces consist of extracts, or long reads in which Generation Y writers address the issues that define and concern them.

uniQure Announces Company Presentations at Upcoming May Conferences – Yahoo Finance

May 1st, 2017

-- Investor breakfast event and webcast at ASGCT on Friday, May 12 at 7:00 a.m. EDT --

LEXINGTON, Mass. and AMSTERDAM, the Netherlands, May 01, 2017 (GLOBE NEWSWIRE) -- uniQure N.V. (QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced company presentations at the following conferences taking place in May:

American Society of Gene and Cell Therapy (ASGCT), May 10 13 2017, at the Marriott Wardman Park hotel in Washington, D.C.

UBS Global Healthcare Conference, May 22 24 2017, at the Grand Hyatt New York, in New York City.

American Biomanufacturing Summit, May 23 24 2017, at the Hyatt Regency Mission Bay Spa & Marina, in San Diego, California.

About uniQure uniQure is delivering on the promise of gene therapy single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary and partnered gene therapies to treat patients with hemophilia, Huntingtons disease and cardiovascular diseases. http://www.uniQure.com.

Go here to read the rest:
uniQure Announces Company Presentations at Upcoming May Conferences - Yahoo Finance

Recommendation and review posted by Bethany Smith

Analyst Activity BTIG Research Reiterates Buy on bluebird bio (NASDAQ:BLUE) – Market Exclusive

May 1st, 2017

Analyst Activity BTIG Research Reiterates Buy on bluebird bio (NASDAQ:BLUE)
Market Exclusive
With its lentiviral-based gene therapy and gene editing capabilities, it has built an integrated product platform with various applications in these areas. The Company's clinical programs in severe genetic diseases include its LentiGlobin product ...

and more »

Read the original post:
Analyst Activity BTIG Research Reiterates Buy on bluebird bio (NASDAQ:BLUE) - Market Exclusive

Recommendation and review posted by simmons

Bone Marrow vs. Fat Derived Stem Cells Continued : Stem …

April 29th, 2017

Whether your adult mesenchymal stem cells come from bone marrow or from fat probably does not make a difference in terms of clinical results. Although some centers claim that bone marrow derived cells are superior to fat derived cells, there is no evidence to substantiate that. Recent studies show that fat derived cells make bone tissue much better than the bone marrow derived cells. Some studies are showing different outcomes but it is important to realize that these studies are all done in petri dishes and may not relate to living organism. Also, it is important that one is not mislead in some marketing materials by the word bone in bone marrow, possibly implying that since this is an orthopedic source it must be better for treating orthopedic conditions such as cartilage regeneration. In fact, the bone marrow is part of the reticulo-endothelial system (makes blood cells) and just happens to be found in the center of bone. The truth is, both bone marrow derived and stromal (from fat) derived stem cells are both effective for regenerative therapy and both have the potential to differentiate into mature functional cartilage. However, stem cells from fat are 100 to 1000 times more plentiful and this makes same day procedures (allowed in the US) much more effective with fat derived cells. The higher numbers of cells in fat leads to better clinical outcomes. Also, the quality of bone marrow declines with age and it has less numbers of cells and less healthy cells compared to the fat. The diminution in quantity and quality of bone marrow cells related to age and chronic illness is well documented. Last but not least, the ease of removing fat from under the skin using a mini-liposuction under local anesthetic is much less invasive and MUCH LESS painful than undergoing bone marrow aspiration to obtain bone marrow cells.

To Read More Click Here

Comprehensive-characterization-of-four-different-populations-of-human-mesenchymal-stem-cells-as-regards-their-immune-properties-proliferation-and-differentiation

Follow this link:
Bone Marrow vs. Fat Derived Stem Cells Continued : Stem ...

Recommendation and review posted by sam

Scientists Can Now Turn Human Skin Cells Into Brain Cells – Wall Street Pit

April 29th, 2017

Researchers at University of California, Irvine (UCI) have developed a method that can transform human skin cells into brain cells. With this amazing feat, scientists may be able to better understand what role inflammation plays in the progression of Alzheimers disease. And this knowledge could lay the groundwork towards developing more effective treatments and therapies to manage the condition.

Before this breakthrough, scientists relied mostly on mice microglia to study the immunology of Alzheimers. Microglia sometimes referred to as Hortega cells are a special kind of cell that can be found in the human brain and spinal cord. The primary role of these cells is to protect the brain and the spine from infections, disease and any invading microbe. They provide immune support for the entire central nervous system by removing dead cells, damaged cells and other debris.

Along this line, microglial cells also help keep healthy cells from degenerating managing inflammation as well as developing and maintaining the integrity of neural networks which is why they are believed to play a special role in delaying the progression of neurodegenerative conditions like Alzheimers.

While studying brain cells from mice is useful, studying the real thing is, of course, more preferable. And the method developed by the UCI team is a step in this direction.

Using skin cells donated by UCI Alzheimers Disease Research Center patients, the UCI team led by Edsel Abud, Mathew Blurton-Jones and Wayne Poon made use of a genetic process to reprogram the skin cells and turn them into induced pluripotent cells (iPSCs) adult cells that are modified to act like embryonic stem cells which can turn into any kind of cell or tissue. The iPSCs were then exposed to a series of differentiation factors which mimicked the developmental origin of microglia. This exposure resulted in cells that are pretty much like human microglial cells.

Instead of continuing to rely on mice microglial cells, scientists now have a more realistic model for studying human disease in order to develop new and better therapies. And they have now started on this new path. They are using the microglial-like cells in 3D brain models so they can study how these cells interact with other brain cells and understand how this interaction impacts the progression of Alzheimers and the development of other neurological conditions.

As explained by Professor Blurton-Jones in a statement they issued: Microglia play an important role in Alzheimers and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimers-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies.

This latest breakthrough is once again proving how important stem cells are in helping understand biological processes, both under normal conditions and under disease-related conditions. Eventually, scientists are bound to stumble on that ultimate discovery that can hopefully be instrumental in combating diseases right at their source, so we can stop dealing with devastating diseases, especially those that affect the brain and threaten a persons life.

The study was recently published in the journal Neuron.

Read more here:
Scientists Can Now Turn Human Skin Cells Into Brain Cells - Wall Street Pit

Recommendation and review posted by simmons

Stem cells edited to fight arthritis: Goal is vaccine that targets … – Science Daily

April 29th, 2017

Science Daily

Stem cells edited to fight arthritis: Goal is vaccine that targets ...
Science Daily
Using CRISPR technology, a team of researchers rewired stem cells' genetic circuits to produce an anti-inflammatory arthritis drug when the cells encounter ...
Fighting arthritis: Researchers edit stem cells to fight inflammationKasmir Monitor
CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis DrugGenetic Engineering & Biotechnology News

all 6 news articles »

See original here:
Stem cells edited to fight arthritis: Goal is vaccine that targets ... - Science Daily

Recommendation and review posted by sam

China Is Racing Ahead of the US in the Quest to Cure Cancer With CRISPR – Gizmodo

April 29th, 2017

On Friday, a team of Chinese scientists used the cutting-edge gene-editing technique CRISPR-Cas9 on humans for the second time in history, injecting a cancer patient with modified human genes in hopes of vanquishing the disease.

In the US, the first planned trials to use CRISPR in people still have not gotten under way. But in China, things appear to be moving relatively quickly.

Last fall, a team at Sichuan Universitys West China Hospital used CRISPR for the first time on an adult with lung cancer. In the new trial, reported by The Wall Street Journal, altered genes were injected into a patient with a rare type of head and neck cancer, called nasopharyngeal carcinoma, at Nanjing Universitys Nanjing Drum Tower Hospital.

The aim is to use CRISPR, which allows scientists to snip out pieces of DNA with greater ease than older gene-editing techniques, to suppress the activity of a gene preventing the patients body from effectively fighting the disease. On Friday, the university announced that the first patient had received an infusion of altered cells, which are taken from their body and altered in a lab before being injected back in.

In all, 20 patients with gastric cancer, nasopharyngeal carcinoma and lymphoma are expected to participate in the trial. Its first phase is expected to conclude next year.

The other Chinese trial, in which scientists modified immune cells to attack lung cancer in 11 patients, expects to release results this year, according to the Journal.

The first US human CRISPR trial is slated to begin this summerat the University of Pennsylvania, after receiving a regulatory stamp of approval to proceed last year. In that trial, scientists plan to genetically alter patients immune cells to attack three different kinds of cancer.

Clearly, a race to cure cancer with CRISPR is underfoot. And right now at least, China seems to be winning.

[Wall Street Journal]

Read the rest here:

China Is Racing Ahead of the US in the Quest to Cure Cancer With CRISPR - Gizmodo

Recommendation and review posted by sam

Irish cardiologists pioneer new treatment for heart patients – Irish Times

April 29th, 2017

Irish cardiologists have found a way to repair damaged cardiac muscle and reduce the risk of future heart failure by injecting a growth promoter into the hearts of heart attack sufferers. Photograph: Getty Images

A team of Irish cardiologists have shown that injecting an insulin-like growth promoter into the hearts of patients who have suffered a severe heart attack can repair damaged cardiac muscle and reduce the risk of future heart failure.

Prof Noel Caplice, Chair of Cardiovascular Sciences at University College Cork, and his cardiologist colleagues at Cork University Hospital successfully tested the growth factor in a clinical trial involving 47 patients who presented at the Cork hospital after experiencing heart attacks.

Prof Caplice said 20 per cent of people who suffer heart attacks have severe ongoing difficulties because of lasting damage to heart muscle even after the best current therapies.

After you have a heart attack, regardless whether you treat it with a stent or whatever, about 20 per cent of patients go on to have poor remodelling heart muscle cells die, you get scar tissue forming and the heart tends to expand and dilates, a bit like a balloon, and you get thinned-out heart muscle.

With that poor remodelling of the heart, the heart as a structure performs much worse, it doesnt work very well in terms of its function that leads to a substantial number of those patients going on to suffer heart failure with an increased risk of death, he said.

However, 10 years ago, Prof Caplice and his team began looking at using stem cells as a means of repairing damaged tissue and they found a protein within the stem cells, IGF 1, previously used to treat congenital dwarfism and growth problems, was leading to the repair of damaged heart muscle.

IGF 1 acts differently to insulin in that it acts on a different receptor in the body and when we inject it, it gets into the heart tissue and it basically stimulates receptors on the surface of the cardiac cells and in about 30 minutes, it sends a survival signal to the heart muscles cells, he said.

What we discovered from the stem cell study was that the concentration of the factor was extremely low so what we did was that we took the purified factor and in studies with pigs we injected them in the context of a heart attack and we found these major remodelling benefits.

Those animal tests were funded by Science Foundation Ireland but four years ago the Health Research Board came on board and the two bodies provided a 1 million grant to allow the treatment be trialled on humans.

Working with a 25-strong team incorporating cardiologists, radiologists, MRI specialists and nurses, Prof Caplice was able to incorporate the IGF 1 trials into the treatment of patients attending CUH with severe cardiac events and over the past three years have trialled it on 47 patients.

Patients received two different low-dose preparations of insulin-like growth factor or placebo in a randomised double-blinded clinical trial, with results showing those who received the higher dose had improved remodelling of their heart muscle in the two-month follow-up after their heart attack.

Prof Caplice said the CUH trials, the results of which he will present at a European Society of Cardiology conference in Paris on Saturday, were the first use of IGF 1 in human hearts and part of its attractiveness was its low dosage ensuring minimal side effects while improving cardiac structure.

Among the beneficiaries was John Nolan from New Ross who suffered a heart attack in December 2014. I feel I was blessed to be asked to be involved; I had confidence that good would come from it, in terms of how they explained it to me. Looking back on it now, I feel it was the right choice.

For Prof Caplice, the challenge now is to expand the trials to several hundred patients possibly across different countries and different healthcare systems to see if the IGF 1 treatment is globally applicable which, if proven to be the case, could lead to regulatory approval within five years.

Read more:
Irish cardiologists pioneer new treatment for heart patients - Irish Times

Recommendation and review posted by Bethany Smith

City of Hope brings together bone marrow transplant recipients and donors for first time – The San Gabriel Valley Tribune

April 29th, 2017

DUARTE >> Evan Braggs, a 32-year-old from Rancho Cucamonga, could not contain his emotions Friday when, for the first time, he met the man who saved his life more than a decade ago.

Its a humbling experience, Braggs said of meeting and embracing his bone marrow donor, Mike Cook, a 49-year-old Marine from Virginia. Braggs and Cook were one of two pairs of donors and recipients meeting for the first time at City of Hopes 41st annual Bone Marrow Transplant Reunion at the hospitals Duarte campus.

Its overwhelming, said Cook. To think that just me saying yes to what I thought was a little thing, turned into such a big thing. I want to thank you (Evan), because you make me a better person.

Sergio Ramirez, 34, of Los Angeles also got to meet and thank in person his donor, Michael Palacios, a 27-year-old from Silver Lake.

My sons were also excited to meet him, especially my youngest who wrote him a poem, and they all have thank-you cards for him, Ramirez said.

Youre a blessing, he said to Palacios.

The yearly event celebrates the work of City of Hope doctors and staff, as well as the success of their transplant program, which has performed more than 13,000 bone marrow, cord blood and stem cell transplants.

More than 4,000 City of Hope transplant recipients, donors, their families and others reunited Friday and were treated to a picnic-style gathering at the campus.

Braggs was a strong young athlete competing in hurdles at Mt. San Antonio College when he was diagnosed with aplastic anemia. The disease prevents a persons blood marrow from making an adequate amount of new blood cells, and can eventually lead to severe heart problems.

The diagnosis was a shock; hed never so much as broken a bone in his life. After several treatments to try to boost his bone marrow production, as well as weekly blood transfusions, doctors determined he needed a bone marrow transplant.

A match was made and Braggs underwent the transplant operation in 2005, while he was on summer break.

Braggs wife, Melina Fregoso, is also a cancer survivor. The couple rode on the City of Hope Rose Parade float together in 2015. She said meeting her husbands donor was an emotional experience.

Im grateful that I got to meet him today, and to give thanks, Braggs said.

Cook, after serving in the Marines for more than two decades, is now a reverend in charge of the mens ministry at Shiloh New Site Baptist Church in Virginia. He said meeting his recipient for the first time Friday allowed him to understand what his donation truly meant.

Cook was stationed at Marine Corps Base Quantico in Virginia when he attended a blood drive and was offered to register for bone marrow donation. When he signed up, Cook thought of his nephew, who was diagnosed with a brain tumor when he was just a toddler.

I thought, if I ever have the chance to save someone, I would, he said.

Just like Cook, the act of giving came naturally to Palacios. He was a volunteer at Childrens Hospital Los Angeles when representatives from Be The Match registry visited. He signed up as soon as he could.

Its just something I do, Palacios said. We dont feel like heroes. If were in a position to help, were happy to do it.

Sergio Ramirez was diagnosed with acute lymphoblastic leukemia. Even after three years of treatment, the disease returned with even greater strength.

Knowing the chances of survival for all patients after relapsing were slim, Ramirez was more concerned with what would happen to his family his wife and three sons.

Ramirez took part in an immunotherapy trial at City of Hope. He responded well to the treatment, and he went into remission. But a bone marrow transplant would be the only thing to prevent the cancer from returning.

Its an amazing feeling every morning I wake up, to hear my kids, to see the sunshine, Ramirez said.

Palacios said he will follow up to make sure he is still on the donor registration list with the hopes that he could have the chance to save another life in the future.

I want to continue to inspire others to donate, he said. After meeting (Ramirez), he can finally say he doesnt have to worry about cancer, and be with his family; that makes me happy and gives me hope.

For more information about City of Hope and bone marrow donor registry, go to http://www.cityofhope.org.

Continued here:
City of Hope brings together bone marrow transplant recipients and donors for first time - The San Gabriel Valley Tribune

Recommendation and review posted by Bethany Smith

The irrefutable success of stem cell treatments Miami’s Community … – Miami’s Community Newspapers

April 29th, 2017

This slideshow requires JavaScript.

In my opinion, one of the hardest things to accept is a new type of medical treatment, particularly when it changes the philosophy, parameters and overall results that we are expecting and basically used to receiving. Stem cells are undoubtedly no exception to this rule.

About six weeks ago, Eduardo K (a Cuban doctor with a Masters Degree from the University of Pittsburg in internal medicine and nephrology), brought his wife Maria to our institute, in order to assess the possibility of using stem cells to cure the severe chronic pain in her ankle; a pain so severe that it was basically hindering her ability to walk. Dr. K also expressed his extreme hesitation and concerns about having his wife involved in an invasive ankle surgery at this stage of her adult life.

However, while conducting our usual examining process, reviewing her medical records and MRIs and thoroughly discussing my overall recommendations about a potential stem cell transplant, I quickly realized that Dr. K was not a true believer in Stem Cell therapies, since he thought that there was not much medical evidence of their actual effectiveness and he ultimately also confessed that his wife had basically dragged him to accompany her to this particular appointment.

As always, I respectfully explained the reality that stem cells actually repair the damaged cartilage in a microscopic type fashion and thus, while this repair process would not be clearly reflected immediately on future X-rays, I assured them that the pain she was suffering from will soon subside and possibly even completely disappear. In addition, I expressed that I was extremely confident that she would also regain her mobility skills after the procedure, even if this improvement could not be easily detected via a radiological image.

Since Marias options were somewhat limited, added to the fact that months of traditional physical therapy, injections, medications and previous surgeries had completely failed her, Dr. K finally agreed to grant his wifes wishes to have her stem cell transplant (from her own bone marrow and fat) performed, although he was still very skeptical about the process and was showing little enthusiasm.

This morning, both of them attended our follow up appointment (six weeks after the procedure) and surprisingly, Maria and Dr. K happily confirmed that she felt at least 60 percent better, something that no previous traditional medical treatments had been able to accomplish. It was then that I explained to them that her stem cells had acted much faster than expected (something that possibly taught Dr. K an interesting lesson).

As we began to say our goodbyes, the doctor told me (first in English, then in Spanish) that: in spite of my skepticism about stem cell therapies, I can personally attest that the successful results seen on my wife have been irrefutable, and with a smile on both of their faces, they gratefully thanked my staff and I for this amazing improvement.

As I continued to replay the words expressed by this doctor over and over in my mind, I quickly realized how truly incredulous human beings tend to be, with most of us often needing to fail several times at accomplishing something before being able to realize and accept that we were truly mistaken in the first place!

So if you, a friend or relative would like to receive Stem Cell or PRP treatments, please call us at 305-598-7777. For information visit: http://www.stemcellmia.com (available in both English and Spanish), or watch our amazing video-testimonies on our YouTube Chanel and also please follow us on Facebook and Twitter. If you would like to ask a question directly to Dr. Castellanos, please do so via his direct email: stemdoc305@gmail.com.

Connect To Your Customers & Grow Your Business

Go here to see the original:
The irrefutable success of stem cell treatments Miami's Community ... - Miami's Community Newspapers

Recommendation and review posted by Bethany Smith

Bone marrow donor forgot he’d registered – Jewish Chronicle

April 29th, 2017

Jewish Chronicle

Bone marrow donor forgot he'd registered
Jewish Chronicle
My phone rang and when I answered they said someone needed my stem cells. They asked me would I still like to donate? I went in the next day for tests and when I was deemed fit and healthy they got me to come back in for the procedure. On Tuesday the ...

Here is the original post:
Bone marrow donor forgot he'd registered - Jewish Chronicle

Recommendation and review posted by sam

Fighting arthritis: Researchers edit stem cells to fight inflammation – Kasmir Monitor

April 29th, 2017

In a major development, researchers have developed a cartilage that fights inflammation caused by arthritis and other chronic conditions, using the gene-editing technique called CRISPR. For the breakthrough, researchers at Washington University School of Medicine converted skin cells from the tails of mice into stem cells. They then used the gene-editing tool CRISPR to remove a gene involved in inflammation and replace it with one that produces anti-inflammatory drug. They called the resulting cells as SMART cells, which stands for Stem cells Modified for Autonomous Regenerative Therapy. "Our goal is to package the rewired stem cells as a vaccine for arthritis, which would deliver an anti-inflammatory drug to an arthritic joint but only when it is needed," said Farshid Guilak, Professor at Washington University School of Medicine, and senior author of a study published online in the journal Stem Cell Reports. "To do this, we needed to create a 'smart' cell," Guilak said. According to the study, SMART cells, develop into cartilage cells that produce a biologic anti-inflammatory drug that could replace arthritic cartilage and simultaneously protect joints and other tissues from damage that occurs with chronic inflammation. Many current drugs used to treat arthritis attack an inflammation-promoting molecule called tumour necrosis factor-alpha (TNF-alpha). But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections. "We want to use our gene-editing technology as a way to deliver targeted therapy in response to localised inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body," Guilak said. The research has been published in the journal Stem Cell Reports.

Link:
Fighting arthritis: Researchers edit stem cells to fight inflammation - Kasmir Monitor

Recommendation and review posted by sam

CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis Drug – Genetic Engineering & Biotechnology News

April 29th, 2017

We have anti-arthritis drugs. What we lack is the ability to deploy them when and where they are needed in the body. The drugs would be far more effective, and occasion fewer side effects, if they were to appear only in response to inflammation, and only in the joints. If the drugs could be delivered so painstakinglyso smartlythey wouldnt have to be administered systemically.

Although conventional drug delivery systems may be unable to respond to arthritic flares with such adroitness, cells may have better luckif they are suitably modified. Stem cells, for example, have been rewired by means of gene-editing technology to fight arthritis. These stem cells, known as SMART cells (Stem cells Modified for Autonomous Regenerative Therapy), develop into cartilage cells that produce a biologic anti-inflammatory drug. Ideally, the new cartilage cells will replace arthritic cartilage, and the biologic will protect against chronic inflammation, preserving joints and other tissues.

SMART cells of this sort were prepared by scientists based at Washington University School of Medicine in St. Louis. The scientists initially worked with skin cells taken from the tails of mice and converted those cells into stem cells. Then, using the gene-editing tool CRISPR in cells grown in culture, they removed a key gene in the inflammatory process and replaced it with a gene that releases a biologic drug that combats inflammation.

Details of this work appeared April 27 in the journal Stem Cell Reports, in an article entitled Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs. The article describes how modified stem cells grew into cartilage and produced cartilage tissue. The engineered cartilage, the scientists reported, was protected from inflammation.

Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- [interleukin-1] or TNF-- [tumor necrosis factor-] mediated inflammation in an autoregulated, feedback-controlled manner, wrote the authors of the Stem Cell Reports article. Our results show that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system.

Many current drugs used to treat arthritisincluding Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab)attack TNF-, an inflammation-promoting molecule. But the problem with these drugs is that they are given systemically rather than targeted to joints. As a result, they interfere with the immune system throughout the body and can make patients susceptible to side effects such as infections.

"We want to use our gene-editing technology as a way to deliver targeted therapy in response to localized inflammation in a joint, as opposed to current drug therapies that can interfere with the inflammatory response through the entire body," said Farshid Guilak, Ph.D., the paper's senior author and a professor of orthopedic surgery at Washington University School of Medicine. "If this strategy proves to be successful, the engineered cells only would block inflammation when inflammatory signals are released, such as during an arthritic flare in that joint."

Dr. Guilak's team encoded the stem/cartilage cells with genes that made the cells light up when responding to inflammation, so the scientists easily could determine when the cells were responding. Recently, the team began testing the engineered stem cells in mouse models of rheumatoid arthritis and other inflammatory diseases.

If the work can be replicated in animals and then developed into a clinical therapy, the engineered cells or cartilage grown from stem cells would respond to inflammation by releasing a biologic drugthe TNF- inhibitorthat would protect the synthetic cartilage cells that Dr. Guilak's team created and the natural cartilage cells in specific joints.

"When these cells see TNF-, they rapidly activate a therapy that reduces inflammation," Dr. Guilak explained. "We believe this strategy also may work for other systems that depend on a feedback loop. In diabetes, for example, it's possible we could make stem cells that would sense glucose and turn on insulin in response. We are using pluripotent stem cells, so we can make them into any cell type, and with CRISPR, we can remove or insert genes that have the potential to treat many types of disorders."

View original post here:

CRISPR-SMART Cells Regenerate Cartilage, Secrete Anti-Arthritis Drug - Genetic Engineering & Biotechnology News

Recommendation and review posted by sam

Another CRISPR Trial Begins – GenomeWeb

April 29th, 2017

Asian Scientist Magazine

Another CRISPR Trial Begins
GenomeWeb
Researchers in China have embarked on a new trial using the gene-editing tool CRISPR/Cas9 to modify human genes to treat cancer patients, the Wall Street Journal reports. For this trial, researchers at Nanjing University have injected the first set of ...
China Is Racing Ahead of the US in the Quest to Cure Cancer With CRISPRGizmodo
CRISPR Used To Modify Multiple Genes In Rice | Asian Scientist ...Asian Scientist Magazine
Insider Selling: Crispr Therapeutics AG (CRSP) Insider Sells ...Transcript Daily
PharmiWeb.com (press release) -Market Exclusive -Wall Street Journal (subscription)
all 11 news articles »

Follow this link:

Another CRISPR Trial Begins - GenomeWeb

Recommendation and review posted by simmons