Archive for the ‘Crispr’ Category

In BriefSickle-cell disease, which afflicts approximately 100,000 Americans with immense pain and shortened life-span, is caused by a single mutated nucleotide within the gene that codes for hemoglobin, making it a top candidate for CRISPR and maybe a cure.

Approximately 100,000 people in the US have sickle-cell disease. Most sufferers are African-Americans, but there are also many Latino patients as well as people of Mediterranean, Middle Eastern, Asian, and Southeast Asian descent who have sickle-cell disease. The disease is painful, and shortens the lifespan of sufferers to about 40 to 60 years.

Although its cause has been understood for more than a century, patients with sickle-cell have historically been underserved by both the pharmaceutical industry and the medical establishment. However, as CRISPR is changing the face of medicine, it may also be changing this lived reality for people with sickle-cell disease, which is caused by a single mutation that is well-studied, making it an appealing candidate for correction with the gene-editing tool.

CRISPR works by cutting into a DNA sequence in a specific place and either deleting a sequence or editing it. In the case of sickle-cell disease, the mutation that causes the illness is a single nucleotide: a T where an A should be within the HBB gene, which codes for hemoglobin. Red blood cells with healthy hemoglobin are the typical disc-shaped red cells seen microscopically, but the mutation causes unhealthy sickle-shaped cells that stick together. Eventually this causes a buildup of cells, blocked blood vessels, and lack of oxygen to different regions in the body along with pain, organ damage, and eventually premature death.

This one mutated nucleotide is an easy fix for CRISPR, which can simply cut and edit that nucleotide. Thus far researchers have had great success with CRISPR in mice and on human sickle cells in the lab, making the next step a clinical trial and maybe a cure.

CRISPR as a tool is not free from safety concerns, but many sickle-cell patients are eager to take part in clinical trials. Lab experiments have shown impressive results, with CRISPR successfully editing about 85 percent of stem cells extracted from sickle-cell patients in order to create healthy red blood cells a great result, given that patients with sickle cells below 30 percent exhibit no symptoms.

Once those healthy cells are reintroduced to the body, they go back to the bone marrow where they create more healthy blood cells for the body. The researchers say these healthy blood cells will proliferate because they will outnumber the sickled cells, particularly since they live 4.5 to 12 times longer.Click to View Full Infographic

Although CRISPR clinical trials have yet to begin in the US, the National Institutes of Health (NIH) is launching a study at the end of August 2017 to explore the opinions people with sickle-cell have about CRISPR technology. If a CRISPR sickle-cell cure does hit the market, access to it will be a defining issue. Ghana-born physician Isaac Odame, who specializes in sickle-cell disease and works at the Hospital for Sick Children in Toronto, told MIT Technology Review that drug costs for hydroxyurea, commonly used to treat the disease, are too expensive for many to afford, even at one to two dollars per day. Scientists and others from all over the world have been meeting and talking about ensuring that people have equal access to CRISPR, although thus far the issue has not passed the discussion stage.

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CRISPR May One Day Cure Sickle-Cell Disease - Futurism

Marcela V. Maus

CRISPR Therapeutics $CRSP is allying with some top immuno-oncology researchers at Mass General to collaborate on some new gene editing working aimed at creating a new and better generation of T cell therapies.

The biotech based in Switzerland with a big research group in Cambridge, MA has tied the partnership knot with Marcela V. Maus, who runs the cellular immunotherapy group at Mass General. Shell be using the biotechs pioneering CRISPR/Cas9 tech to see how it works in building a new-and-improved T cell therapy just as the original models appear poised to hit the market later in the year.

This is by no means the first such gene editing effort in I/O, but it does reflect the companys continuing effort to build a pipeline of I/O drugs. They hired Jon Terrett (a vet at the South San Francisco-based cancer biotech CytomX) to run the operation on I/O back in February and struck a deal with MaSTherCell SA on making their CAR-T CTX101, targeting CD19 cancers. And they believe that they have potential for next-gen therapies that can work in both liquid as well as solid tumors the Holy Grail in I/O now.

A little more than a year ago Carl June and his team at the University of Pennsylvania, backed by The Parker Institute, obtained permission to run the first gene editing experiment for an immunotherapy with human subjects. That project involved using CRISPR in 18 subjects, extracting T cells and then editing them to add a protein that recognizes cancer cells and issues an attack order, then edit out a protein that interferes with the attack and finally disable the cloaking mechanism cancer cells use to hide from the immune system.

We have already seen the profound benefit that T cell therapies can have for certain patients with a specific set of tumor types, said Maus in a prepared statement.Now the potential with gene editing, and specifically CRISPR/Cas9, exists to create improved versions of these cells that may work for a wider variety of patients with a more diverse set of tumor types. Im glad to see the commitment CRISPR Therapeutics is making to this area, and am excited to collaborate with them.

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Building up its I/O ops, CRISPR Therapeutics allies with Marcela Maus at Mass General - Endpoints News

CRISPR keeps cancer in check

SPL

By Michael Le Page

The CRISPR genome editing revolution continues to advance at an astounding pace. As many as 20 human trials will be under way soon, mostly in China, New Scientist has learned.

One of these trials will involve the first-ever attempt to use CRISPR to edit cells while they are inside the body. The aim is to prevent cervical cancers by targeting and destroying the genes of the human papillomavirus (HPV) that cause tumour growth. This study is due to begin in July at the First Affiliated Hospital of Sun Yat-Sen University in China.

Gene therapy, which involves adding extra genes to cells, was first used to cure people in 1990, but it is mainly useful for treating rare genetic disorders. In contrast, gene-editing, which involves altering existing genes inside cells, promises to treat or cure a much wider range of conditions, from HIV infection to high blood cholesterol.

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One of these trials will involve the first-ever attempt to edit cells insidethe body

The first gene-editing trial in humans started in 2009. Doctors removed immune cells from people with HIV, disabled the gene for the CCR5 receptor which the virus uses to get into cells and returned the HIV-resistant cells to the body. The treatment appears to keep HIV in check.

But subsequent progress in gene editing was slow because developing a way to target each particular sequence is costly and time consuming. All that changed in 2012 when CRISPR genome editing was developed, making it cheap and easy to target almost any sequence.

The first clinical trial involving CRISPR began at the West China Hospital in Chengdu in October 2016. Doctors removed immune cells from the blood of a person with lung cancer, used CRISPR to disable a gene called PD-1 and then returned the cells to the body.

PD-1 codes for an immune cell off switch. Tumours can flip this switch to prevent immune cells attacking so if immune cells lack the PD-1 switch then cancer cells cannot manipulate them. However, there is a risk that the always on immune cells could begin attacking healthy cells.

The lung cancer trial isnt due to finish until 2018, but other teams are forging ahead. Clinical trial registries show that a dozen more trials that will disable PD-1 with CRISPR are planned in China. These target conditions including breast, prostate, bladder, oesophageal, kidney, colorectal and Epstein-Barr virus-associated cancers.

The HPV trial, meanwhile, will break new ground. Instead of editing cells outside the body, a gel containing DNA coding for the CRISPR machinery will be applied to the cervix. The CRISPR machinery should leave the DNA of normal cells untouched, but in cells infected by HPV, it should destroy the viral genes, preventing them from turning cancerous.

Targeting HPVs seems a sensible approach if they can deliver the genome-editing components to sufficient numbers of cells, says Robin Lovell-Badge of the Crick Institute in the UK.

It is tricky to do these experiments in animals as they are not infectable by HPV, says Bryan Cullen of Duke University Medical Center in North Carolina, whose group also hopes to use gene editing to get rid of HPV. But there is a risk of off-target mutations leading to cancer, he warns.

If these trials are successful, it could benefit millions of people. Vaccination against HPV is now possible, but there is no way to get rid of the virus in people who have it already. It can cause mouth, throat and anal cancers in both sexes, as well as being the main cause of cervical cancer.

While the HPV trial looks set to be the first to use CRISPR to edit cells inside the body, it may not be the first ever such use of genome editing. Three trials getting underway in the US will use another genome editing method known as zinc finger nucleases to add genes to liver cells to try to treat haemophilia B, and Hurler and Hunter syndromes.

A further four planned CRISPR trials involve changing immune cells to make them better at killing cancers. First, a virus will be used to add a gene to immune cells that makes them attack specific tumours creating so-called CAR-T cells. Then two or more genes usually including PD-1 will be disabled with CRISPR to make the cells even more effective.

Such UCART19 cells have already saved the lives of two girls, but these cells were created with an older gene-editing method. Now a clinical trial is due to start in the UK. Our lab is moving over to CRISPR, team leader Waseem Qasim of University College London told a meeting in February.

Two similar UCART19 trials areplanned in China, with another in the US. Trials are also planned for Duchenne muscular dystrophy, says Lovell-Badge, butthese are probably some way from starting.

This article will appear in print under the headline Boom in gene-editing clinical trials

We clarified what is unique about the reported trials.

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Boom in human gene editing as 20 CRISPR trials gear up | New ...

In BriefCRISPR Therapeutics has teamed up with General Hospital of Massachusetts to further-widen CRISPR's near-ubiquitous applications. Within this two-year collaboration, CRISPR/Cal9 will also be used in T cell cancer therapies.

In a recent development, CRISPR Therapeutics, the subsidiary of CRISPR AG, has signed onto a two-year research collaboration with Massachusetts General Hospital (MGH), to research the use of CRISPR/Cas9 in T cell cancer therapies.

This comes on the heels of a seemingly-endless list of advances. Two weeks ago, the CRISPR/Cas9 gene editing tool successfully removed genetic disorders from human embryos and additionally,successfully extracted HIV from a living organism. It was used to develop semi-synthetic organisms, targeted the command center of cancer, and even coerced superbugs to kill themselves on the genetic level.

The application of CRISPR/Cas9 to T cell therapies is expected to address unmet needs in hematologic and solid tumors, masses which from the cells are typically extracted and programmed to recognize and attach to. Leading the scientific work at MGH is the director of the Cellular Immunotherapy Program, Marcela V. Maus, MD, Ph.D. Anticipating the benefits of the collaboration, head of Immuno-oncology Research and Translation at CRISPR Therapeutics, Jon Terrett, Ph.D., told GlobeNewswire:

It is becoming increasingly clear that CRISPR/Cas9 can play a major role in enabling the next generation of T cell therapies in oncology. By combining our gene editing capabilities with Dr. Maus pioneering expertise in T cell therapy, we hope to accelerate our progress toward making these therapies a reality for patients suffering from cancer.

This partnership is CRISPR Therapeutics latest step toward advancing immuno-oncology. Terrett was brought aboard in February of this year as the companys leader in this regard.

Mausadded:

We have already seen the profound benefit that T cell therapies can have for certain patients with a specific set of tumor types. Now the potential with gene editing, and specifically CRISPR/Cas9, exists to create improved versions of these cells that may work for a wider variety of patients with a more diverse set of tumor types. Im glad to see the commitment CRISPR Therapeutics is making to this area, and am excited to collaborate with them.

Expect to see CRISPR/Cas9 expand its applications to include a more diverse spectrum of tumor types and molecular targets, as the revolutionary medical technology carries on.

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CRISPR Therapeutics Joins Hospital For Cancer Treatment Tests - Futurism

The first test-tube baby made headlines around the world in 1978, setting off intense debate on the ethics of researching human embryos and reproductive technologies. Every breakthrough since then has raised the same questions about designer babies and playing God but public response has grown more subdued rather than more engaged as assisted reproductive technologies have become increasingly sophisticated and powerful.

As the science has advanced, doctors are able to perform more complex procedures with better-than-ever success rates. This progress has made in vitro fertilization and associated assisted reproductive technologies relatively commonplace. Over one million babies have been born in the U.S. using IVF since 1985.

And Americans acceptance of these technologies has evolved alongside their increased usage, as weve gotten used to the idea of physicians manipulating embryos.

But the ethical challenges posed by these procedures remain and in fact are increasing along with our capabilities. While still a long way from clinical use, the recent news that scientists in Oregon had successfully edited genes in a human embryo brings us one step closer to changing the DNA that we pass along to our descendants. As the state of the science continues to advance, ethical issues need to be addressed before the next big breakthrough.

Louise Brown was born in the U.K. on July 25, 1978. Known as the first test-tube baby, she was a product of IVF, a process where an egg is fertilized by sperm outside of the body before being implanted into the womb. IVF opened up the possibility for infertile parents to have their own biologically related children. But Browns family was also subjected to vicious hate mail, and groups opposed to IVF warned it would be used for eugenic experiments leading to a dystopian future where all babies would be genetically engineered.

The reaction in the U.S. had another layer to it when compared to other developed countries. Here, research on embryos has historically been linked to the debate on abortion. The 1973 Supreme Court decision to make abortion legal in Roe v. Wade fueled anti-abortion groups, who also oppose research on human embryos.

Embryonic research and procedures offer the hope of eliminating devastating diseases, but scientists also destroy embryos in the process. Under pressure from these groups over the ethical implications of embryo creation and destruction, Congress issued a moratorium in 1974 on federally funded clinical research on embryos and embryonic tissue, including on IVF, infertility and prenatal diagnosis. To this day, federal funds are still not available for this type of work.

In hindsight, the sharp media attention and negative response from anti-abortion groups to IVF didnt accurately represent overall public opinion. The majority of Americans (60 percent) were in favor of IVF when polled in August 1978, and 53 percent of those polled said they would be willing to try IVF if they were unable to have a child.

So while the intense media coverage at the time helped inform the public of this new development, the insensitive labeling of Louise Brown as a test-tube baby and warnings about dystopian results didnt stop Americans from forming positive opinions of IVF.

In the nearly 40 years since IVF was introduced for use in humans, scientists have developed several new technologies from freezing eggs to genetically testing embryos before implantation that have improved patient experience as well as the chances that IVF will result in the birth of a baby. The announcement of each of these breakthroughs has resulted in flurries of media attention to the ethical challenges raised by this type of research, but there has been no consensus social, political or scientific on how to proceed.

Americans general opinion of assisted reproductive technologies has remained positive. Despite opposition groups efforts, surveys show that Americans have separated out the issue of abortion from embryonic research. A Pew Research Center poll from 2013 revealed that only 12 percent of Americans say they personally consider using IVF to be morally wrong. Thats a significant decrease from the 28 percent of respondents in 1978 who replied that they opposed the procedure for being not natural. In addition, the 2013 poll showed that twice as many Americans (46 percent) said they do not personally consider using IVF to be a moral issue compared to the number of Americans (23 percent) who said they personally do not consider having an abortion to be a moral issue.

Although most Americans dont think of embryonic research and procedures like IVF as a moral issue or morally wrong, the introduction of new technologies is outpacing Americans understanding of what they actually do.

Polls from 2007-2008 showed that only 17 percent of respondents reported that they were very familiar with stem cell research, and that there was a relative absence of knowledge about even the most prominent of the embryo-research issues. When Americans are asked more specific questions that explain IVF, they show less support for certain procedures, like freezing and storing eggs or using embryos for scientific research.

In light of recent developments, surveys show that nearly 69 percent of Americans have not heard or read much or know nothing at all about gene editing. Additionally, support for gene editing depends on how the technology will be used. A majority of Americans generally accept gene editing if the purpose is to improve the health of a person, or if it will prevent a child from inheriting certain diseases. The scientists in Oregon used a gene-editing technique that allowed them to correct a genetic defect in human embryos that causes heart disease. This type of progress falls into the category that most Americans would support.

But the technique thats used to make this correction, known as CRISPR-Cas9, can potentially be used for editing genes in other ways, not just to eliminate diseases. The success of the Oregon team opens the door to many possibilities in gene editing, including ones unrelated to health, such as changes to appearance or other physical characteristics.

Advancements in assisted reproductive technologies have happened rapidly over the last few decades, leading to over five million births worldwide. But as common as these procedures have become, scientists are not yet in agreement over how to integrate CRISPR and gene editing to the IVF toolkit. There are concerns about changing the genomes of human embryos destined to be babies, particularly since any modifications would be passed on to future generations. Scientific committees have noted that decisions on whether and how to use gene editing should be revisited on a regular basis. The newest breakthrough with CRISPR is providing us with one of those opportunities.

We should focus our attention on answering the ethical questions that have long gone unanswered: What are the boundaries to this type of research? Who decides what is an ethical use of CRISPR? What responsibility do we have to people affected by genetic conditions? Who pays for these medical procedures? How will this research and potential clinical use be regulated?

The successful use of assisted reproductive technologies has skyrocketed in the last decade, making Americans complacent about some of the ethical concerns that these procedures raise. Its important that we engage with these issues now, before gene editing becomes as familiar to us as IVF.

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Will CRISPR fears fade with familiarity? - The Conversation US

AUGUST 23, 2017

A CRACK IN CREATION is not The Double Helix. They are both stories of revolutionary biological advances, told by one of the discoverers, but The Double Helix feels like a novel. And, like a historical novel, it was eventually understood to be based on real events but not always reliable history.

A Crack in Creation is also not a history that is, a detailed and precise explanation of who did what and when to produce CRISPR/Cas9, this centurys biggest biological discovery to date. That history awaits its Horace Freeland Judson, whose magisterial The Eighth Day of Creation provided a gripping blow-by-blow account of the birth and adolescence of molecular biology, or its Robert Cook-Deegan, whose The Gene Wars illuminated the beginnings of the Human Genome Project.

Nor is this a how to book for aspiring do-it-yourself CRISPR users; or a deep analysis of the ethical, legal, and social issues CRISPR and its progeny will raise; or a legal analysis of the already (in)famous CRISPR patent fight; or a look at the unresolved Nobel Prize race. And it is not a gossipy inside look at the people intimately involved in CRISPRs invention.

So what is A Crack in Creation? It is an essential start to educating the public.

Humans use of the bacterial defense mechanism called clustered regularly interspaced short palindromic repeats (CRISPR), with or without CRISPR associated protein 9 (Cas 9) along with the technologies that eventually will modify or displace it is of vast importance. Thats not because it is the first way we have found to edit DNA. It misses that distinction by over 40 years. But it is the first truly fast, cheap, easy, and accurate way to do so. It is biotechnologys Model T. The Model T was not, by several decades, the first automobile, but it transformed cars from expensive, unreliable, inconvenient, and rare objects to something everyone could, and soon did, own. It is the change in degree, not in kind, that has transformed the world we live in (nowhere more than California). Similarly, humans have been manipulating living organisms, including ourselves, at least since the dawn of modern man, but CRISPR is the change in degree that turns gene editing from expensive, unreliable, inconvenient, and rare to ubiquitous. It vastly increases our powers to edit all life, including our own.

A Crack in Creation tells the story of CRISPR through the eyes and in the voice of Jennifer Doudna, the UC Berkeley biochemist who was a central figure in harnessing it. (The co-author, Samuel Sternberg, is Doudnas former graduate student.) It divides elegantly into two four-chapter parts, plus prologue and epilogue. The first part describes what CRISPR is and how it was discovered; and the second sets out CRISPRs possible uses in the environment and medicine, and in editing humankind.

It is not, however, the first publication to recount the origins of CRISPR. Indeed, as with the double helix, the identity of the originators is contested. In January 2016, Eric Lander, director of the Cambridge, Massachusettsbased Broad Institute (jointly owned by Harvard and MIT), published a 7,200-word essay titled The Heroes of CRISPR in Cell, one of three leading journals for bioscience publications. It was widely criticized for minimizing the contributions of Doudna and one of her key collaborators, Emmanuelle Charpentier, and highlighting instead the work of Feng Zhang, a researcher at the Broad (and hence Landers employee). As well as triggering, fairly or not, debate over the issue of sexism in science, Landers piece was particularly controversial in that the publication never mentioned its authors conflicts of interest, not just in promoting Zhang as CRISPRs hero, but because of the very expensive patent fight over CRISPR between the Broad Institute and Doudnas employer, the University of California (UC).

This said, what both Lander and Doudna do well is reveal the complex, interlocking, and thoroughly international nature of todays bioscience. They acknowledge the work of a dizzying number of contributors to CRISPR. The first publication to show that CRISPR could be used to edit bacterial DNA was Doudna and Charpentiers Science article in June 2012 but, by that time, scores of researchers had already been exploring what was regarded as a tantalizing bacterial curiosity.

In his Cell article, Lander writes that [t]he story starts in the Mediterranean port of Santa Pola, on Spains Costa Brava, with Francisco Mojica who published a report in 2005 on the existence of, and possible immune system function of, certain odd, largely palindromic, DNA repeats in several bacterial species. Researchers at a yogurt company, Danisco, also played important roles, as did Sylvain Moineau in Quebec and John van der Oost from the Netherlands. Even before her first meeting with Doudna in March 2011, Charpentier and her lab at the University of Ume in Sweden had also contributed to the development of the CRISPR system.

Virginijus iknys, a Lithuanian researcher, greatly improved researchers understanding of the proteins bacteria used with CRISPR. He saw some of the possibilities of CRISPR as a tool and submitted a paper to Cell on the topic on April 6, 2012. Cell rejected his paper, which was eventually published on September 4, 2012, in the Proceedings of the National Academy of Sciences. In the meantime, Doudna and Charpentiers paper was submitted to Science on June 8 and published 20 days later.

But if this is more or less the beginning of the CRISPR discovery story, it is certainly not the end.

Feng Zhang, a brilliant young researcher at the Broad, had spent much of 2011 and 2012 working on a way to use CRISPR in mammalian cells. Zhang submitted his first CRISPR publication on October 5, 2012. Later that month, George Church, an exceptionally wide-ranging and creative Harvard researcher, submitted a paper on using CRISPR in human cells, which Science published in the same issue as Zhangs on January 3, 2013.

This summary does not come close to mentioning all the laboratories involved in discovering and developing CRISPR and does not even begin to talk about the vital contributions of the post-docs and graduate students in those labs, all of them highlighted in A Crack in Creation.

Whose version is closest to the true history of CRISPR? Landers history was widely attacked and A Crack in Creation has already been criticized in a review in Nature for downplaying Zhangs role (though it mentions him more than Lander mentioned Doudna). I suspect neither Lander nor Doudna and Sternberg could tell the full story for at least one sad reason lawyers probably wouldnt let them. Their employers are locked in a patent struggle. The details of who did, said, or knew what when could be crucial to its outcome. How many changes in the manuscripts came as a result of lawyers comments? Probably more than a few.

In fairness, A Crack in Creation never promises to be the definitive history of CRISPR much less a story of all its heroes. It tells Doudnas CRISPR story, as well as the authors thoughts on its potential uses and implications. These uses and implications make up the books second part, The Task. It begins with the use of CRISPR in the non-human world for agricultural purposes and beyond, including the ongoing development of gene drives, an important adaptation of CRISPR that can speed the spread of desired genetic changes in sexually reproducing species, as well as plausible speculation about future unicorns (in this case, the mythical animal). It then addresses the medical applications of CRISPR to living people in the form of so-called somatic gene editing, intended to heal their bodies without changing their eggs or sperm and so not affecting future generations. The authors rightly view this as the least controversial use of CRISPR. The last chapters address what has become the stickiest question for most people: the use of CRISPR to make changes in the genome of the human germline (eggs and sperm) that can be inherited from generation to generation.

Doudnas interest in these last issues is neither new nor shallow. In October 2014, I was invited to a small meeting she was organizing in Napa Valley the following January to discuss the ethical issues of CRISPR. (Coincidentally, this was almost exactly 40 years after the famous 1975 Asilomar meeting to assess safety issues of the first gene editing, recombinant DNA.) The Napa meeting involved about a dozen prominent scientists including Paul Berg and David Baltimore, the two Nobel Prize winners who helped organize the Asilomar meeting and two law professors who work in the field, Alta Charo from the University of Wisconsin and myself. Doudnas genuine concern was evident, not just in calling the meeting but in her active and thoughtful participation in it. And human germline genome editing was clearly the focus of that concern.

The Napa meeting reached consensus surprisingly quickly: the somatic cell uses of CRISPR should be pursued actively, but human germline modifications needed more thought. Doudna took the lead in drafting a commentary, signed by the meetings participants and several others, which Science published in March 2015.

The commentary made four recommendations about human germline editing:

The Science article was not alone. Nature had published a commentary on human gene editing the week before, endorsing somatic cell uses of genome editing, but rejecting germline changes. And two weeks later, an obscure journal published an article in which Chinese scientists reported their (slightly) successful efforts using CRISPR to edit human embryos.

The Chinese group had carefully used human embryos that were not viable and thus could never become babies, but the article still set off a firestorm. One of its results was a US National Academies of Sciences, Engineering, and Medicine initiative to study genome editing. A major part of that initiative was an International Summit on Human Gene Editing held in Washington, DC in December 2015, with additional sponsorship from the Chinese Academy of Sciences and the UK Royal Society. At its end, the summits planning committee (not the sponsoring academies) issued its conclusions, roughly echoing the March Science commentary.

As A Crack in Creation usefully points out, the debate over germline modification is not new. The issue was discussed in print at least 30 years before CRISPR was imagined. But a sense of urgency and some specificity about both the likely intervention and the societies into which it will be launched helps focus discussions. Since the International Summit (and submission of the last manuscript of the book), the National Academies alone have published at least three relevant reports two concerning non-human uses of CRISPR in October 2016 and March 2017, and the third, issued in February 2017 on Valentines Day, on CRISPR and humans, endorsing somatic cell uses of CRISPR and opening the door for possible germline editing for medical reasons.

A Crack in Creation hints that the discussions thus far have modified Doudnas views. Like the February 2017 report, the book shows some openness to human germline modification, at least for addressing clearly genetic diseases.

Personally, I think we focus too much on human germline genome modification. There is no human germline genome there are over seven billion of them, each changing slightly by mutation in every generation. Editing out rare, disease-causing DNA variations or replacing them with the more common safe variants hardly seems radical. The real concerns for germline or somatic human gene editing should be about enhancements (as opposed to disease), but that is just one part of a much wider conversation about all kinds of biological, electronic, and mechanical enhancements. The combination of our great concern about the safety of babies and our ignorance regarding enhancing genetic variants, however, means we have time to get this right. But were way behind in regulating the use of CRISPR in non-humans. The medical, practical, and political constraints around human babies do not exist for mosquito babies, let alone genetically modified microbes or plants. For the moment, we need to concentrate on this much less constrained use of CRISPR, which is already beginning.

Doudna called for discussions about the uses of CRISPR in Napa in January 2015 and A Crack in Creation amplifies that plea, providing the interested public with the background critical to such discussions. But CRISPR has raised two other interesting questions, which, though not discussed in the book, are worth mentioning: the Nobel Prize and the patent fight.

A Crack in Creation says nothing about the likely Nobel Prize for CRISPR, but CRISPR junkies regularly discuss it. A Nobel Prize in either Chemistry or in Medicine and Physiology seems almost certain, and will likely be granted soon. But who will receive it?

Scores of people in many countries contributed to its discovery, but Nobel Prizes in the sciences are limited to not more than three people. Doudna and Charpentier should be shoo-ins, for their own insights, for the work of their labs, and for their first publication. Plausible other candidates include at least Mojica, iknys, Zhang, and Church but four into one wont go.

Many have read Landers Cell article as an effort to tilt the third spot toward his faculty member, Zhang, but the fight over the patent rights for CRISPR could also influence who wins the prize. A Crack in Creation mentions the patent fight only once, as a disheartening twist to what had begun as collegial interactions and genuine shared excitement about the implications of the research. But the patent cases over CRISPR have been unusual, and unusually fascinating, from the beginning. (For more details see various pieces by Jacob Sherkow, the law professor who has followed this most closely.)

In December 2012, Zhang and others (meaning the Broad Institute on behalf of Zhang and others) filed a patent application on the use of CRISPR in any cells from complex organisms, called eukaryotic cells, which include everything from algae to us, as opposed to prokaryotic cells (bacteria and archaebacteria) and viruses. Doudna and Charpentiers patent application had been filed seven months earlier, claiming the use of CRISPR in all cells. But the Broad paid for and got a special expedited patent procedure so that its patent application, though filed after the UCs, was granted in April 2014, before the UCs was decided.

A year later, in April 2015, the UC invoked an interference proceeding, asking the Patent and Trademark Office (PTO) to resolve an apparent inconsistency in patent applications and determine who was the first inventor. In February 2017, the PTO ruled in favor of Zhang and the Broad. But the UC has appealed this decision, and even if it stands, it is possible that the Doudna and Charpentier patent and the Zhang patent will be held valid, in which case someone who wanted to use CRISPR in eukaryotic cells, including human cells, would need licenses from both UC and the Broad.

Furthermore, all patents are limited to the jurisdiction that granted them. US patents have no force outside the United States. This past March, the European Patent Organization granted CRISPR patents to UC, as have the patent authorities in China and the United Kingdom. So we could have a world where the Broad seems to control important US uses and the UC the European, British, and Chinese uses. The rest of the world is, at this point, up for grabs.

What does all this mean? In terms of the ultimate ownership of the most basic CRISPR patent rights, stay tuned. It is too soon to tell. But, in a larger sense, I dont think it matters.

This is mainly a fight about money: about which American universities will make money, and how much of it, off some uses of CRISPR. If the money goes to the UC system, as a Californian I would be pleased. But the question of who profits shouldnt change the adoption of CRISPR. That is, as long as either entity uses a good licensing strategy. Of course, even that may not matter. The CRISPR patents will give the players ownership of some approaches, but they will be of little value if novel approaches are developed. Already various inventors have come up with alternatives to Cas9 as part of the CRISPR complex. Bacteria invented CRISPR billions of years ago and have had time, and selective pressure, to invent variations on it. The harder the Broad or UC try to enforce rigorous patent terms, the more they encourage researchers to invent around their patents. The more they tighten their grip, the sooner the money will slip through their hands.

This raises the more fundamental question of why the CRISPR patent fight is happening at all. Like many people, I initially thought the UC and the Broad would settle their patent dispute quickly. Each would take a certain percent of the royalties for their combined patents and be happy not least because they would avoid tens of millions of dollars of expense, months of distraction for their researchers, and years of uncertainty. If one of the institutions involved were a novice in technology licensing, then it might get greedy and seek a complete victory, but neither the UC system nor the Broad (and certainly not the Broads owners, Harvard and MIT) are novices. They have some of the most experienced and sophisticated technology licensing offices in the world.

So why are they spending so much money on this fight? It might, in part, relate to the Nobel Prize. If Lander really wants to bolster Feng Zhangs case for winning a CRISPR Nobel Prize, then he may think that having Feng win some or all of the patents will be helpful. That seems a bit far-fetched, and yet it could be one factor in the Broads litigation strategy. If so, it is not clear whether it will succeed, even if the Broad patents eventually sweep the field. The Nobel Prize decision-makers need not follow the patent office of any country.

In the end, the history, the prizes, and the patents dont really matter. The structure of DNA would have been discovered without Watson and Crick, and CRISPR did not require Doudna and Charpentier (or Zhang). The discoveries, not those who make them, are important and those discoveries are only important as they affect people. CRISPR heralds a new era of massively increased human control over life, one that will affect every person on Earth, directly or indirectly, and much of the rest of our planets biosphere. If humans are to have any chance of harnessing its benefits, avoiding its risks, and using it in ways consistent with our values and cultures, then we all not just the scientists, ethicists, and patent lawyers need to understand something about CRISPR and its implications. A Crack in Creation is a great place to start.

In the interest of full disclosure, the author has met, been on panels with, and likes Doudna, Charpentier, Zhang, Church, and many of the other scientists discussed in the review. He also has lectured the last three summers in a CRISPR program held by the Innovative Genomics Institute at UC Berkeley for modest honoraria.

Henry T. Greely is a professor of Law, and professor by courtesy of Genetics, at Stanford University, where he directs its Center for Law and the Biosciences and Program in Neuroscience and Society. He is an expert on the ethical, legal, and social implications of advances in the biosciences.

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CRISPR, Patents, and Nobel Prizes - lareviewofbooks

Next-Generation Immunotherapies

CRISPR Therapeutics interest in next-generation T-cell cancer immunotherapies comes as both Kite Pharma and Novartis await FDA decisions on their CAR-T immuno-oncology treatments, with the companies emerging as leading developers of CAR-T therapies. Last month, Novartis won an FDA advisory committees unanimous recommendation of approval for Novartis leukemia-fighting treatment CTL019 (tisagenlecleucel), a CAR-T therapy developed through a collaboration between the pharma giant and researchers from the University of Pennsylvania launched in 2012.

CRISPR Therapeutics drug development efforts also include partnerships with Bayer and Vertex Pharmaceuticals intended to develop CRISPR-based therapeutics in diseases with high unmet need. CRISPR Therapeutics and Bayer have formed a $335 million-plus joint venture, Casebia Therapeutics, to develop treatments aimed at curing blood disorders, blindness, and congenital heart disease.

CRISPR Therapeutics is among four companies to have licensed CRISPR technology for which a European patent was granted in March to the Regents of the University of California (UC), the University of Vienna, and Emmanuelle Charpentier, Ph.D., a director at the Max-Planck Institute in Berlin.

The European patent holders are appealing a February 15 decision by the Patent Trial and Appeal Board (PTAB), which sided with the Broad Institute of MIT and Harvard in the bitter legal battle over who invented the gene-editing platform. The PTAB found no interference in fact between 12 patents related to CRISPR technology that list as inventor Feng Zhang, Ph.D., of the Broad, and a patent application by Dr. Charpentier and Jennifer Doudna, Ph.D., of UC Berkeley.

The European patent holders have cited decisions by other countries to grant them patents for CRISPR/Cas9 in all settings, including eukaryotic cellsincluding the U.K., nearly 40 other countries that are members of the European Patent Convention, and Asia-Pacific nations such as Australia, New Zealand, Singapore, and China.

Joining CRISPR Therapeutics in licensing the European-patented CRISPR technology are Caribou Biosciences, ERS Genomics, and Intellia Therapeutics.

Also last month, the European Patent office granted Cellectis a patent to use CRISPR in T cells, to be issued in August and valid until 2034. Were not a company thats here to block the other [companies], Cellectis chairman and CEO Andre Choulika, Ph.D., told GEN. Were here to develop products on our sidebut, if there are people that are interested in using CRISPR in T cells, were definitely open to talk to them.

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CRISPR Therapeutics, MGH Partner to Develop T-Cell Cancer Therapies - Genetic Engineering & Biotechnology News

CrisprCon is not a place where spandexed, beglittered, refrigerator drawer fans come together for an all-you-can-eat celebration of unwilted produce. No. Crispr-Cas9 (no E), if you havent been paying attention, is a precise gene editing tool thats taken the world by storm, promising everything from healthier, hangover-free wine to cures for genetic diseases. Like, all of them. And CrisprCon is where people come not to ask how to do those things, but rather, should we? And also, whos the we here?

On Wednesday and Thursday, the University of California, Berkeley welcomed about 300 peoplescientists, CEOs, farmers, regulators, conservationists, and interested citizensto its campus to take a hard look at the wnderenzyme known as Cas9. They discussed their greatest hopes and fears for the technology. There were no posters, no p-values; just a lot of real talk. You can bet it was the first Crispr conference to sandwich a Cargill executive between a septagenarian organic farmer and an environmental justice warrior. But the clashing views were a feature, not a bug. "When you feel yourself tightening up, that's when you're about to learn something," said moderator and Grist reporter, Nathanael Johnson.

Which, to be honest, was totally refreshing. Serious conversations about who should get to do what with Crispr have been largely confined to ivory towers and federal agencies. In February the National Academy of Sciences released a report with its first real guidelines for Crispr, and while it suggested limitations on certain applicationslike germline modificationsit was largely silent on questions outside of scientific research. What sorts of economies will Crispr create; which ones will it destroy? What are the risks of using Crispr to save species that will otherwise go extinct? Who gets to decide if its worth it? And how important is it ensure everyone has equal access to the technology? Getting a diverse set of viewpoints on these questions was the explicit goal of CrisprCon

Why was that important? Greg Simon, director of the Biden Cancer Initiative and the conferences keynote speaker, perhaps said it best: Crispr is not a light on the nation, its a mirror. In other words, its just another technology thats only as good as the people using it.

Panel after panel took the stage (each one, notably, populated with women and people of color) and discussed how other then-cutting-edge technologies had failed in the past, and what history lessons Crispr users should not forget. In the field of conservation, one panel discussed, ecologists failed to see the ecosystem-wide effects of introduced species. As a result, cane toads, red foxes, and Asian carp created chaos in Australia and New Zealand. How do you prevent gene drivesa technique to spread a gene quickly through a wild populationfrom running similarly amok?

From the agricultural field, the lessons were less nebulous. First-generation genetically modified organisms failed to gain public support, said organic farmer Tom Willey, because they never moved agriculture in a more ecologically sustainable direction and it never enhanced the quality of food people actually ate. At least, noticeably so. Instead, most modifications were to commodity crops like corn and soy to improve their pest resistance or boost yields.] It was a convenience item for farmers, he said. And a profit center for corporations. In order for gene-edited foods to avoid the same fate, companies like Monsanto, Dupont Pioneer, and Cargill, who have already licensed Crispr technologies, will need to provide a more tangible value than corn you can spray the bejeezus out of. Like say, extra-nutritious tomatoes, or a wine with 10-times more heart-healthy resveratrol and fewer of the hangover-causing toxins.

The presence of executives from each of these three companies signaled that theyre serious about not making the same mistakes they did in the 90s when GMOs first came to market. Back then we were only talking to farmers, said Neal Gutterson, vice president of R&D at Dupont Pioneer during a break between panels. I cant remember anyone going to anything like this or casting as wide a net in our discussions with the public.

Of all the fields Crispr will touch, medicine is the one most primed for disruption. So its of great concern to conference-goers that Crispr doesnt become a technology only for the haves and not the have-nots. Shakir Cannon, founder of the Minority Coalition for Precision Medicine, pointed out the myriad ways doctors and researchers have exploited people of color in the name of scientific advancement, while neglecting diseases that hit underserved communities the hardest. In a breakout session on Wednesday, Rachel HaurwitzCEO of Caribou Biosciences, one of the big three Crispr companiesasked Cannon and his colleague, Michael Friend, how industry leaders could help make sure that doesnt happen. First, you have to build trust with communities, said Friend, whose work focuses on sickle cell anemia. But we think Crispr could be a real turning point.

Still, CrisprCon was just more talkwhich the field has seen a lot of recently. Crisprs co-discoverer Jennifer Doudna has taken a step back this past year from her lab at Berkeley to travel the world and discuss the importance of coming to what she calls a global consensus on appropriate uses for gene editing technologies. And in her opening address on Wednesday, the standing-room-only auditorium heard a line shes trotted out many times before. I've never seen science move at the pace its moving right now, Doudna said. Which means we cant put off these conversations." The conversations happening at CrisprCon were all the right ones. But action, whether in the form of regulations, laws, or other populist social contracts, still feels a long way off.

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Crispr Fans Dream of a Populist Future for Gene Editing | WIRED - WIRED

In BriefCRISPR co-discoverer Jennifer Doudna stressed the importance of using the technology with proper consideration at CrisprCon this week.

The CRISPR gene editing tool has already been used to perform some incredible feats of science, from manipulating the social behavior of ants to making superbugs kill themselves. Its an incredibly powerful asset, but this week at CrisprCon, there was plenty of discussion about where we should draw a line on its usage.

Ive never seen science move at the pace its moving right now, said CRISP co-discoverer Jennifer Doudna, who has spent recent months touring the world campaigning for a global consensus on appropriate implementations of gene-editing technologies. Which means we cant put off these conversations.

CRISPR has already been used to edit harmful conditions out of animals and even viable human embryos. From this point, it wouldnt take a great leap to start using the technology to enhance healthy organisms which is why now is the time for discussions about the consequences.

While medical uses of CRISPR are perhaps the most ethically urgent, the conversation about its usage goes beyond medicine. Companies like Monsanto and Cargill have already licensed CRISPR technologies to help with their agricultural efforts. However, early attempts at genetically modified crops struggled to gain mainstream acceptance, and thats something these firms need to keep in mind as they implement the latest techniques.

It was a convenience item for farmers, observed organic farmer Tom Wiley at the convention, according to Wired. And a profit center for corporations. To combat genetically modified foods perception problem, companies using CRISPR will have to make sure that the technology benefits the consumer, not just the production process.

The convention addressed CRISPR usage in many different fields: from the importance of ensuringit is used to address the widest range of medical conditions as possible, to the potentially damaging effects of gene drives on a delicate ecosystem.

Science is moving at a rapid pace, and CRISPR is too but if we dont carefully consider which applications are safe and valid, it could quickly cause as many problems as it solves.

Crispr is not a light on the nation, its a mirror, said CrisprCon keynote speaker Greg Simon, director of the Biden Cancer Initiative;Wiredreporter Megan Molteni interpreted those words as,its just another technology thats only as good as the people using it.

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CRISPR Co-Discoverer: "I've Never Seen Science Move at the Pace ... - Futurism

Science and ethics experts took part in a first-of-its-kind conference on the role of gene editing, and nearly half of the sold-out crowd was involved in the food and agriculture sector. CRISPRcon a summit named for the genome editing technique known as clustered regularly interspaced short palindromic repeats (CRISPR) brought together a diverse set of panelists to discuss this emerging technology.

CRISPR technology allows precise changes to be made to the DNA of living cells, which holds the potential to eradicate diseases, transform agriculture and enable massive leaps forward in environmental and life sciences. Through a series of keynote speakers, panels and interactive discussions, CRISPRcon offered a single forum for those with a stake in gene editing to share ideas, ask and answer questions and explore the path forward.

Since the CRISPR-Cas9 technology was invented five years ago by a team led by Dr. Jennifer Doudna, professor of chemistry and of molecular and cell biology at the University of California-Berkeley, and her colleague Emmanuel Charpentier, it has revolutionized biomedical and agricultural research while fueling angst about questionable applications, such as designer crops, farm animals and humans.

Its really a very cross-cutting technology, Doudna told attendees.

In fact, she said unlike earlier ways of manipulating genetic information in cells, the thing that makes CRISPR particularly powerful is the fact that it really is a democratizing tool. Its a technology that is easy enough to use and to employ that its accessible to a wide range of people, Doudna said.

It has been possible to globally adopt the technology for use in any organism, she added.

Doudna discussed applications of gene editing, including producing cattle with no horns, finding ways to treat human genetic diseases of the blood, cancer-related research, generating animals that would be better organ donors for humans, as well as plant and crop research.

The agriculture industry was represented among speakers. Thomas Titus, a pork producer from Illinois, was one of only two farmers who presented among the scientific experts, physicians, patients, environmentalists, consumers and community leaders.

Gene editing will have great impact on the future of farming, and especially on livestock production, Titus said. Although in its very early stages of development and acceptance, gene editing could ultimately be used to make pigs resistant to diseases, thereby improving food safety, animal welfare and the environmental impact of agriculture.

Titus, who raises pigs and also grows grain on his Illinois farm, was part of a panel discussing where CRISPR technology could take society by 2050. His appearance was supported by the pork checkoff and the National Pork Producers Council. Other panelists included representatives from the Center for Genetics & Society, the Institute for the Future, PICO National Network and The Breakthrough Institute.

Todays consumer is educated and asking questions about where their food comes from and how it is raised, Titus said. Thats why I welcome every chance I get to talk about todays pork production. I appreciated the opportunity to once again open my barn doors to share how I raise pigs with these key influencers in food production.

Other topics addressed during the conference included societal perception and acceptance of CRISPR application in surgery, human health and food production and conservation.

Doudna said just understanding the science is a challenge for many people, but then they also have to understand how the technology is going to affect them.

She encouraged scientist to take a very active role in engaging in conversation about gene editing, adding that its always challenging to explain technical work in a non-technical setting.

Its important to appreciate what the technology can and cannot do. Its not a magical technology; its not perfect, she said. While there are still a number of aspects of the technology that are still at the beginning phase, Doudna said the field is an incredibly fast-moving area. Ive never seen science move at the pace it is moving right now, she added.

When asked how to know when to use the cutting-edge technique, Doudna said the recommendation is to look for situations where there really is no other reasonable way to deal with a genetic disease other than gene editing. When you think about it that way, those situations are rare, she noted.

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Genome editing CRISPR technique takes center stage | Feedstuffs - Feedstuffs

News that U.S. scientists led by Oregon Health and Sciences University biologist Shoukrat Mitalipov have used the gene-editing technique known as CRISPR to modify the DNA of human embryos has led to renewed debate over human genetic engineering. Although scientists in China and the United Kingdom have already used gene editing on human embryos, the announcement that the research is now being done in the United States makes a U.S. policy response all the more urgent.

The scientists created 131 embryos that carried a genetic mutation that causes hypertrophic cardiomyopathya condition that can lead to sudden and unexpected heart attacks but has few other symptomsand attempted to correct the mutation in 112 of them (leaving 19 as unmodified controls).By injecting the CRISPR complex together with the sperm cells that carried the mutation, rather than injecting CRISPR into already fertilized embryos, the scientists were able to successfully correct the mutated genes in 72 percent of the embryos.Whether the embryos were successfully or unsuccessfully treated, all were destroyed after the researchers were finished with the study.

Much of the debate over CRISPR has been framed around concerns over the creation of so-called designer babieschildren genetically engineered to possess desirable traits that will then be passed on to subsequent generations. Some science writers and journalists have tried to downplay these concerns by noting that the gene editing was done only for basic research, rather than as an attempt to create a genetically engineered human. Writing in The New York Times, Pam Belluck argued that even if scientists do modify the genes of human embryos, fears that embryo modification could allow parents to custom order a baby with Lin-Manuel Mirandas imagination or Usain Bolts speed are closer to science fiction than science.

Those downplaying concerns also argue that preexisting practices such as the abortion of fetuses diagnosed with Down syndrome or the selective discarding of embryos diagnosed with genetic disease through preimplantation genetic diagnosis (PGD) are exactly the reason gene-editing

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CRISPR and the Ethics of Human Embryo Research - Foreign Affairs

ST. LOUIS Monsanto Company has forged an agreement with ToolGen, Inc., a biotechnology company specializing in genome editing, to use ToolGens CRISPR technology platform to develop agricultural products.

The companies announced Aug. 16 that they have reached a global licensing agreement for Monsanto to access ToolGens suite of CRISPR intellectual property for use in plants.

CRISPR stands for clustered regularly interspaced short palindromic repeats. Its a relatively new way to modify an organisms genome by precisely delivering a DNA-cutting enzyme to a targeted region of DNA. The resulting modification can delete or replace specific DNA pieces, thereby promoting or disabling certain traits.

The companies noted that gene-editing technologies, like CRISPR, offer agriculture researchers significant advantages over existing plant breeding and biotechnology methods due to their versatility and efficiency.

This agreement further expands Monsantos broad portfolio of gene-editing tools that can be used to develop improved and sustainable crops, said Tom Adams, Ph.D., vice president of biotechnology for Monsanto.

As a company we remain committed to the development of safe, sustainable and high-quality crops, and look forward to leveraging the CRISPR platform.

Additional terms of the agreement were not disclosed.

In January, Monsanto announced an agreement with the Broad Institute of MIT and Harvard for the nonexclusive use of its CRISPR-Cpf1 genome-editing technology, which is different from the CRISPR-Cas9 system.

Related articles:

CRISPR mushroom created at Penn State a GMO game-changerMonsanto agreement with Broad for CRISPR systemDuPont Pioneer scientists demonstrating potential of CRISPR-Cas for agricultureResearch finds probiotics may combat disease

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Monsanto adds another CRISPR platform to genetic toolbox - Farm ... - Farm and Dairy

A staple of bad science fiction, mutant ants have been more of a figment of imagination rather than scientific reality. Weve genetically altered mice and fruit flies, but growing mutant ants has eluded scientists due to the complex life cycle of the little critters. Now two teams announced that they managed to edit out certain genes from lab ants, altering their behavior.

The team from Rockefeller University published a paper outlining how they removed orco - a gene that plays a key part in an ants odor receptors. Deleting the gene by using theCRISPR-Cas9 technique resulted in the ants losing about 90% of their olfaction. This made them unable to socialize. The ants also changed in other ways, showing affected behavior. They laid very few eggs, wandered aimlessly, and showed poor parenting.

The other team, including scientists from NYU, Vanderbilt University, University of Pennsylvania, and Arizona State University, also used CRISPR to delete the orco protein in ants to affect their communication through pheromones, causing an "aberrant social behavior and defective neural development."

You can read their paper here.

Researchers modified the ability of the ants to detect pheromones though porous hairs on their antennae. Credit: Rockefeller University.

This kind of interference with the social behavior of ants is considered a success because of the difficulty in altering the nature of insects with such a sophisticated social structure. NYU Professor Claude Desplan, who was involved in one of the studies called the modified ant they created the first mutant in any social insect.

While ant behavior does not directly extend to humans, we believe that this work promises to advance our understanding of social communication, with the potential to shape the design of future research into disorders like schizophrenia, depression or autism that interfere with it, said Desplan.

Why edit ant genes at all? Daniel Kronauer, author of the Rockefeller University study, says there are interesting biologic questions you can only study in ants.

It was well known that ant language is produced through pheromones, but now we understand a lot more about how pheromones are perceived, saysKronauer. The way ants interact is fundamentally different from how solitary organisms interact, and with these findings we know a bit more about the genetic evolution that enabled ants to create structured societies.

Check out this animation of how Kronauer and his colleagues tracked color-coded ants, while using an algorithm to analyze the resulting behavior.

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Scientists Use CRISPR Gene Editing to Create the World's First ... - Big Think

We are one step closer to having pig organ transplants, a new study shows.

Using the genetic cut-and-paste tool CRISPR, scientists have removed DNA-based viruses that usually infect pig organs, raising the chances that these animal organs could be safely transplanted into human patients one day, a process known as xenotransplantation.

Still, that doesn't mean pig organ transplants are just around the corner; scientists would still need to change other elements of pig transplants to ensure the human body doesn't reject them.

Currently, there is a dramatic shortage in the number of organ transplants available for people who need them, and many people die before they receive one. Animals such as pigs could theoretically supply an unlimited source of such organs. But immune incompatibilities and viruses that are incorporated into the pig genome, called porcine endogenous retroviruses (PERVs), have made it very likely that such pig organs would never take on their own. [11 Body Parts Grown in the Lab]

To get around those PERVs, scientists at eGenesis, a bioengineering company in Cambridge, Massachusetts, used CRISPR-Cas 9, a genetic tool that cuts the genome wherever it's targeted, to remove 62 PERVs in pig cells in culture. The team then injected these cells into pig egg cells and generated baby pigs. They then used genetic testing to show that the pigs did not contain any trace of these PERVs.

"Although we have focused in this paper on the applications to xenotransplantation, we envision, more generally, that the synergistic combination of CRISPR-Cas technology with anti-apoptosis treatment may also be used to enable large-scale genome engineering in primary cells for a broad range of applications," the researchers wrote in the study, which was published yesterday (Aug. 10) in the journal Science.

Originally published on Live Science.

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Pig-to-Human Transplants: CRISPR Gene Editing May Make This Possible - Live Science

Pig organs are the same size as human organs and function pretty much the same way, but pig to human transplantation has long been an elusive goal for researchers due to fear of activating dormant viral diseases in the pigs cells.

But theres hope on the horizon, thanks to a new study out in Science today involving CRISPRd piglets. Researchers in the study used the gene-editing technology to effectively cut out a porcine endogenous retrovirus (PERV) commonly found throughout pig bodies.

The findings represent an important breakthrough in the potential for xenotransplantation, or the use of animal organs in humans.Currently there are more than 117,000 men, women and children on the donor waiting list in the U.S., 22 of whom die each day from lack of a matching donor. The ability to use a pig heart, lungs or other body parts could shore up the shortage and save numerous lives.

This is the first time researchers have been able to demonstrate they were able to inactivate PERV and open the way for xenotransplantation without cross-species contamination.

The company behind the study, eGenesis, which was founded by Harvard genome godfather George Church and Luhan Yang, says it used a technique involving a combination of CRISPR and a method preventing primary cell death during the editing process to inactivate all 62 copies of PERV in piglet embryos. Those embryos were then implanted in sows, growing to fully formed piglets, free of PERV.

CRISPR holds enormous potential to wipe out diseases in both humans and animals, upend our food system and has many other applications we likely dont see yet. Just last week, U.S. scientists were able to demonstrate they could successfully CRISPR out a faulty heart gene mutation in human embryos. However, there is still a lot to take into account before applying the technology to fully formed human beings.

eGenesis says it will continue to monitor the piglets for any long-term effects and, according to Yang, will also further engineer the PERV-free pig strain to deliver safe and effective xenotransplantation.

Read more here:
CRISPR'd pigs offer hope for the human organ transplant shortage - TechCrunch

This photograph shows Ooceraea biroi workers tagged with color dots for individual behavioral tracking. Credit: Daniel Kronauer The Rockefeller University

The gene-editing technology called CRISPR has revolutionized the way that the function of genes is studied. So far, CRISPR has been widely used to precisely modify single-celled organisms and, more importantly, specific types of cells within more complex organisms. Now, two independent teams of investigators are reporting that CRISPR has been used to manipulate ant eggsleading to germline changes that occur in every cell of the adult animals throughout the entire ant colony. The papers appear August 10 in Cell.

"These studies are proof of principle that you can do genetics in ants," says Daniel Kronauer, an assistant professor at The Rockefeller University and senior author of one of the studies. "If you're interested in studying social behaviors and their genetic basis, ants are a good system. Now, we can knock out any gene that we think will influence social behavior and see its effects."

Because they live in colonies that function like superorganisms, ants are also a valuable model for studying complex biological systems. But ant colonies have been difficult to grow and study in the lab because of the complexity of their life cycles.

The teams found a way to work around that, using two different species of ants. The Rockefeller team employed a species called clonal raider ants (Ooceraea biroi), which lacks queens in their colonies. Instead, single unfertilized eggs develop as clones, creating large numbers of ants that are genetically identical through parthogenesis. "This means that by using CRISPR to modify single eggs, we can quickly grow up colonies containing the gene mutation we want to study," Kronauer says.

The other team, a collaboration between researchers at New York University and the NYU School of Medicine, Arizona State University, the Perelman School of Medicine at the University of Pennsylvania, and Vanderbilt University. , used Indian jumping ants (Harpegnathos saltator). "We chose this species because they have a peculiar feature that makes it easy to transform workers into queens," says Claude Desplan, a Silver Professor at NYU and one of the senior authors of the second study. If the queen dies, the young worker ants will begin dueling for dominance. Eventually, one of them becomes a "pseudoqueen"also called a gamergateand is allowed to lay eggs.

"In the lab, we can inject any worker embryo to change its genetic makeup," Desplan says. "We then convert the worker to a pseudoqueen, which can lay eggs, propagate the new genes, and spawn a new colony."

Desplan, co-senior author Danny Reinberg, a Howard Hughes Medical Institute investigator at NYU Langone, and Shelley Berger, the Daniel S. Och University Professor in the departments of Cell and Developmental Biology and Biology at Penn, began studying these ants several years ago as a way to learn about epigenetics, which refers to changes in gene expression rather than changes in the genetic code itself. "The queens and the worker ants are genetically identical, essentially twin sisters, but they develop very differently," Desplan says. "That makes them a good system for studying epigenetic control of development."

The gene that both research teams knocked out with CRISPR is called orco (odorant receptor coreceptor). Ants have 350 genes for odorant receptors, a prohibitively large number to manage individually. But due to the unique biology of how the receptors worka great stroke of luck, in this casethe investigators were able to block the function of all 350 with a single knockout. "Every one of these receptors needs to team up with the Orco coreceptor in order to be effective," says Waring Trible, a student in Kronauer's lab and the first author of the Rockefeller study.Once the gene was knocked out, the ants were effectively blind to the pheromone signals they normally use to communicate. Without those chemical cues, they become asocial, wandering out of the nest and failing to hunt for food.

More surprisingly, knocking out orco also affected the brain anatomy in the adult animals of both species. In the same way that humans have specialized processing centers in the brain for things like language and facial recognition, ants have centers that are responsible for perceiving and processing olfactory cues that are expanded compared to other insects. But in these ants, the substructures of these sensory centers, called the antennal lobe glomeruli, were largely missing.

"There are many things we still don't know about why this is the case," Kronauer says. "We don't know if the neurons die back in the adults because they're not being used, or if they never develop in the first place. This is something we need to follow up on. And eventually, we'd like to learn to what extent the phenomenon in ants is similar to what's going on in mammals, where brain development does depend to a large extent on sensory input."

"Better understanding, biochemically speaking, how behavior is shaped could reveal insights into disorders in which changes in social communication are a hallmark, such as schizophrenia or depression," Berger says.

In a third related study from the University of Pennsylvania, researchers led by Roberto Bonasio altered ant behavior usingthe brain chemical corazonin. When corazonin is injected into ants transitioning to become a pseudo-queen, it suppresses expression of thebrain protein vitellogenin. This change stimulated worker-like hunting behaviors, while inhibiting pseudo-queen behaviors, such as dueling and egg deposition.

The video will load shortly.

Further, when the team analyzed proteins the ant brain makes during the transition to becoming a pseudo-queen, they found that corazonin is similar to a reproductive hormone in vertebrates. More importantly, they also discovered that release of corazonin gets turned off as workers became pseudo-queens. Corazonin is also preferentially expressed in workers and foragers from other social insect species. In addition to corazonin, several other genes were expressed in a worker-specific or queen-specific way.

"Social insects such as ants are outstanding models to study how gene regulation affects behavior," says Bonasia, an assistant professor of Cell and Developmental Biology. "This is because they live in colonies comprised of individuals with the same genomes but vastly different sets of behaviors."

Explore further: 'Princess pheromone' tells ants which larvae are destined to be queens

More information: 1. Cell, Trible et al: "orco mutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants." http://www.cell.com/cell/fulltext/S0092-8674(17)30772-9 , DOI: 10.1016/j.cell.2017.07.001

2. Cell, Yan et al: "An engineered orco mutation produces aberrant social behavior and defective neural development in ants" http://www.cell.com/cell/fulltext/S0092-8674(17)30770-5 , DOI: 10.1016/j.cell.2017.06.051

3. Cell, Gospocic et al.: "The neuropeptide corazonin controls social behavior and caste identity in ants" http://www.cell.com/cell/fulltext/S0092-8674(17)30821-8 , DOI: 10.1016/j.cell.2017.07.014

Journal reference: Cell

Provided by: Cell Press

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Researchers use CRISPR to manipulate social behavior in ants - Phys.Org

In BriefResearchers hope to find out more about the biochemistry of disorders affecting socialization, having successfully provoked asocial behavior in ants.

Researchers have used the CRISPR technique to manipulate the social activities of ants for a study that will be published in Cell. Two independent teams knocked out the orco (odorant receptor coreceptor) gene in entire colonies of ants, which negated their ability to perceive pheromone signals they use to communicate. Without those cues, they began to exhibit asocial behaviors like leaving the safety of the nest and declining to aid efforts to hunt for food.

Ants possess a whopping 350 genes for odorant receptors, but as they all need to liaise with the orco gene to be effective, they could all be knocked out at once. The two teams chose different ants based on two distinct strategies for proliferating this edit among the colony.

One group chose a species that has no queens, instead procreating using unfertilized eggs that mature as clones, producing ants that are genetically identical. CRISPR was used to edit lone eggs, which produced an entire colony with the desired modification.

Meanwhile, the other team of researchers selected a species known for an unusual trait that sees worker ants graduate to the role of egg-laying pseudoqueen in the event that the former queen dies. The chosen worker ant had its genetic makeup modified being converted into a pseudoqueen and prompted to spawn a new colony.

The social interactions of ants are fascinating because of the way a colony acts as a single entity. And as such, these amalgamate superorganisms can potentially tell us a lot about the way we humans interface with one another.Click to View Full Infographic

The researchers observed that disabling the orco gene resulted in certain substructures from the ants central processing centers going missing. These parts of the brain are essential to their olfactory communications, and its not known exactly why they disappeared. Symptomatically, this is analogous to a number of human mental disorders.

The hope is that further research into the biochemistry of ant colony behavior could reveal more about disorders that affect social communication, like depression or schizophrenia. If we can better understand this process as it occurs in an ants brain, and then that of the invisible hand moving the colony as superorganism, we might shine a light on how similar changes that affect mammals.

Original post:
Researchers Used CRISPR to Manipulate the Social Activities of Ants - Futurism

On track to file for clinical trial application(CTA) for lead program in beta-thalassemia in 2017Rapid progress in immuno-oncology including a lead program in allogeneic CAR-T cell therapyExpanded foundational and therapeutic intellectual property positionStrong financial position to support development of pipeline and fund operations

ZUG, Switzerland and CAMBRIDGE, Mass., Aug. 10, 2017 (GLOBE NEWSWIRE) -- CRISPR Therapeutics, (NASDAQ:CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today reported financial results for the second quarter ended June 30, 2017 and provided a business update.

CRISPR Therapeutics has had a very productive first half of the year across all aspects of our business and we remain on track to achieve the goals we set at the beginning of the year, said Dr. Rodger Novak, CEO of CRISPR Therapeutics. Our lead program in hemoglobinopathies remains on track for a CTA submission in late 2017, with clinical trials beginning in 2018. We are advancing our immuno-oncology portfolio and other in vivo applications supported by the signing of key collaborations, and we remain focused on building an organization with top notch talent.

Recent Highlights and Outlook:

Lead hemoglobinopathies program remains on track to file CTA by year-end 2017, and begin clinical trials in 2018. CRISPR Therapeutics highlighted the most recent progress of its hemoglobinopathies program during the Presidential Symposium at the 22nd European Hematology Association Annual Congress in June. The data presented provided further support for CRISPRs approach of re-creating the natural condition of hereditary persistence of fetal hemoglobin (HPFH) that is protective in sickle cell disease and in beta-thalassemia. The presentation described the ability to re-create specific HPFH gene variants in the intended target tissue, human CD34+ stem cells, and demonstrated that these gene variants increase the expression of protective fetal hemoglobin. The data presented continues to support the development of the lead product candidate for beta-thalassemia and sickle cell disease and the Company remains on track to file a clinical trial application (CTA) in Europe by year-end 2017 for beta-thalassemia.

Advancing immuno-oncology program through lead allogeneic CAR-T program and collaborations. CRISPR Therapeutics is rapidly advancing its lead immuno-oncology program through pre-IND studies and process development for manufacturing. The lead program, CTX101, is an allogeneic CAR-T cell therapy being developed for the treatment of CD19-positive malignancies. CRISPR has demonstrated the use of its proprietary gene editing technology to make targeted modifications in T cells, thereby creating an allogeneic or off-the-shelf product that is designed for a broader patient population and addresses several challenges of the current generation of autologous therapies. In June, the Company announced an agreement with MaSTherCell SA, a full-service contract development and manufacturing organization, to develop and manufacture CTX101 under cGMP conditions for use in future clinical trials. Beyond its lead program, CRISPR announced a research collaboration with Neon Therapeutics (Neon) to explore the combination of its CRISPR gene editing platform with Neons neo-antigen platform to develop novel T cell therapies.

Advancing in vivo applications through in-licensing and collaborations. In May, CRISPR Therapeutics announced the signing of an exclusive license to a family of proprietary lipid nanoparticle (LNP) technologies from the Massachusetts Institute of Technology. Utilizing this technology, the Company demonstrated high-efficiency elimination of a target protein produced in the liver. These data were presented at the Cold Spring Harbor Laboratory Genome Engineering conference in July. Additionally, CRISPR and its collaborators at the University of Florida were awarded a two-year grant from Target ALS Foundation, a non-profit organization dedicated to accelerating new treatments for ALS, to support discovery and validation of CRISPR/Cas9-based therapeutic approaches for ALS and frontotemporal dementia (FTD). In April, CRISPR announced a collaboration with StrideBio, a leading developer of adeno-associated virus (AAV) based technologies, to co-develop new vectors for the in vivo delivery of CRISPR/Cas9-based therapeutics to various organ systems.

Strengthened international intellectual property around the foundational and therapeutic CRISPR/Cas9 gene editing technology. Following recent patent grants in the United Kingdom and Europe that broadly cover its in-licensed gene editing technology, CRISPR Therapeutics announced it has received a similarly broad patent from Chinas State Intellectual Property Office (SIPO), and it has recently received additional grants or notices of allowance from Australia, New Zealand and Singapore. The claims being granted in these jurisdictions are directed to CRISPR/Cas9 single-guide gene editing methods for modifying target DNA in both non-cellular and cellular settings, including cells from vertebrate animals such as human or mammalian cells as well as composition of matter and system claims for use in any setting, including claims for the use in producing medicine for treating disease. The growing international recognition of the broad applicability of CRISPRs patent applications for use in all settings, including in human and other eukaryotic cells, continues to reinforce the Companys position as a leader in the rapidly evolving gene editing industry.

In the U.S., CRISPR announced, jointly with its licensors and other sub-licensees, that it had filed the opening brief to the U.S. Court of Appeals for the Federal Circuit (the Federal Circuit) seeking reversal of a decision by the U.S. Patent and Trademark Offices Patent Trial and Appeal Board (PTAB) in an interference proceeding relating to CRISPR/Cas9 gene editing technology. In the appeal, University of California (UC) requests reversal of the PTABs decision terminating the interference between certain CRISPR/Cas9 patent claims owned by UC and claims of the Broad Institute, Harvard University and the Massachusetts Institute of Technology (collectively, Broad). In parallel with the appeal, CRISPR is pursuing other patent applications in the U.S. to pursue patents claiming the CRISPR/Cas9 technology and its use in non-cellular and cellular settings, including eukaryotic cells.

Organizational growth and senior leadership additions. CRISPR Therapeutics continues to enhance its team by attracting and hiring experts across all critical functions including research and development, manufacturing, clinical operations and other areas. In June, CRISPR appointed James R. Kasinger as General Counsel. Mr. Kasinger will oversee the companys corporate legal and governance matters. Prior to joining CRISPR, Mr. Kasinger was General Counsel and Secretary at Moderna Therapeutics. Recently, in August, CRISPR announced the appointment of Dr. Tony Ho as the new Head of Research and Development for the company. Tony brings over 20 years of experience in the industry across both research and development in multiple therapeutic areas. Most recently, Tony was SVP and Head of Oncology Integration and Innovation at AstraZeneca. Currently CRISPR Therapeutics employs 114 people across its three locations. In July, the Companys global headquarters was moved from Basel to Zug, Switzerland, as approved by shareholders at the Companys recent annual meeting.

Financial Results for Three and Six Months Ended June 30, 2017 (U.S. GAAP):

As of June 30, 2017, CRISPR Therapeutics had $272.3 million in cash as compared to $315.5 million in cash as of December 31, 2016. Based on its current operating plan, CRISPR expects its existing cash resources will be sufficient to fund operating expenses and capital expenditure requirements for at least the next two years.

Three Months Ended June 30, 2017

CRISPR Therapeutics reported a net loss of $22.3 million for the three months ended June 30, 2017 as compared to a net loss of $17.2 million for the three months ended June 30, 2016. The increase in net loss of $5.1 million resulted primarily from an increase in loss from operations of $4.7 million, an increase in the provision for income taxes of $0.3 million and an increase in other expense of $0.1 million.

Collaboration revenue for the three months ended June 30, 2017 was $3.6 million, compared to $0.8 million for the three months ended June 30, 2016. The increase of $2.8 million was primarily due to an increase in research and development service revenue under our collaboration agreements with Casebia and Vertex of $1.5 million and $1.3 million, respectively.

Research and development expenses for the three months ended June 30, 2017 were $17.1 million, compared to $8.6 million for the three months ended June 30, 2016. The increase of $8.5 million was primarily attributable to increases of $3.2 million of variable process and platform development costs, $2.1 million of facilities costs including rent and utilities at our new research facility, $2.1 million of employee-related costs and $1.1 million of employee stock based compensation costs.

General and administrative expenses were $7.8 million for the three months ended June 30, 2017, compared to $8.8 million for the three months ended June 30, 2016. The decrease of $1.0 million was primarily due to decreases of $2.0 million in costs associated with a 2016 passive foreign investment company (PFIC) tax liability and $0.9 million in employee stock based compensation costs. The decreases were offset by increases of $1.0 million in employee-related costs to support our overall growth, $0.6 million in professional and consulting expenses, and $0.3 million in facilities costs including rent and utilities at our new facility.

Six Months Ended June 30, 2017

CRISPR Therapeutics reported a net loss of $43.8 million for the six months ended June 30, 2017, compared to a net loss of $25.6 million for the six months ended June 30, 2016. The increase in net loss of $18.2 million resulted primarily from an increase of $13.8 million in loss from operations, an increase of $0.5 million in the provision for income taxes, an increase of $0.3 million in the loss from equity method investment, an increase of $0.1 million in other expense and a decrease of $11.5 million on the gain on extinguishment of the convertible loan with Vertex offset by a decrease in interest expense of $8.0 million from the convertible loan with Bayer.

Collaboration revenue for the six months ended June 30, 2017 was $6.3 million, compared to $1.3 million for the six months ended June 30, 2016. The increase of $5.0 million was primarily due to an increase in research and development service revenue under our collaboration agreements with Casebia and Vertex of $2.6 million and $2.4 million, respectively.

Research and development expenses for the six months ended June30, 2017 were $31.9 million, compared to $14.6 million for the six months ended June 30, 2016. The increase of $17.3 million was primarily attributable to increases of $5.9 million in variable process and platform development costs, $4.7 million in facilities costs including rent and utilities at our new research facility, $4.5 million in employee-related costs, and $2.2 million in employee stock based compensation costs.

General and administrative expenses were $16.4 million for the six months ended June 30, 2017, compared to $14.9 million for the six months ended June30, 2016. The increase of $1.5 million was primarily due to the increases of $2.1 million in employee-related costs to support our overall growth, $1.5 million in facilities costs including rent and utilities at our new research facility, and $0.3 million in employee stock based compensation costs. The increases were offset by a reduction of $2.4 million in our 2016 PFIC tax obligation and franchise taxes on the convertible preferred stock financings.

About CRISPR Therapeutics

CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 gene editing platform. CRISPR/Cas9 is a revolutionary technology that allows for precise, directed changes to genomic DNA. The company's multi-disciplinary team of world-class researchers and drug developers is working to translate this technology into breakthrough human therapeutics in a number of serious diseases. Additionally, CRISPR Therapeutics has established strategic collaborations with Bayer AG and Vertex Pharmaceuticals to develop CRISPR-based therapeutics in diseases with high unmet need. The foundational CRISPR/Cas9 patent estate for human therapeutic use was licensed from the company's scientific founder Emmanuelle Charpentier, Ph.D. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Forward-Looking Statement

Certain statements set forth in this press release constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the intellectual property coverage and positions of the company, its licensors and third parties, and the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. You are cautioned that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: uncertainties regarding the intellectual property protection for our technology and intellectual property belonging to third parties; uncertainties inherent in the initiation and completion of preclinical studies for the Companys product candidates; availability and timing of results from preclinical studies; whether results from a preclinical trial will be predictive of future results of the future trials; expectations for regulatory approvals to conduct trials or to market products; and those risks and uncertainties described under the heading Risk Factors in the companys most recent annual report on Form 10-K, and in any other subsequent filings made by the company with theU.S. Securities and Exchange Commission(SEC), which are available on the SECs website atwww.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made.

More:
CRISPR Therapeutics Announces Second Quarter 2017 Financial Results and Provides Business Update - GlobeNewswire (press release)

On August 2nd, scientists achieved a milestone on the path to human genetic engineering. For the first time in the United States, scientists successfully edited the genes of a human embryo. A transpacific team of researchers used CRISPR-Cas9 to correct a mutation that leads to an often devastating heart condition. Responses to this feat followed well-trodden trails. Hype over designer babies. Hope over new tools to cure and curb disease. Some spin, some substance and a good dose of science-speak. But for me, this breakthrough is not just about science or medicine or the future of humankind. Its about faith and family, love and loss. Most of all, its about the life and memory of my brother.

Jason was born with muscle-eye-brain disease. In his case, this included muscular dystrophy, cerebral palsy, severe nearsightedness, hydrocephalus and intellectual disability. He lived past his first year thanks to marvels of modern medicine. A shunt surgery to drain excess cerebrospinal fluid building up around his brain took six attempts, but the seventh succeeded. Aside from those surgeries complications and intermittent illnesses due to a less-than-robust immune system, Jason was healthy. Healthy and happy very happy. His smile could light up a room. Yet, that didnt stop people from thinking that his disability made him worse off. My family and those in our religious community prayed for Jason. Strangers regularly came up to test their fervor. Prayer circles frequently had his name on their lists. We wanted him to be healed. But I now wonder: What, precisely, were we praying for?

Jasons disabilities fundamentally shaped his experience of the world. If praying for his healing meant praying for him to be normal, we were praying for Jason to become someone else entirely. We were praying for a paradox. If I could travel back in time, Id walk up to young, devout Joel and ask: How will Jason still be Jason if God flips a switch and makes him walk and talk and think like you? The answer to that question is hard. Yes, some just prayed for his seizures to stop. Some for his continued well-being. But is that true of most? Is that what I was praying for?

The ableist conflation of disability with disease and suffering is age-old. Just peruse the history of medicine. Decades of eugenic practices. Sanctioned torture of people with intellectual disability. The mutilation of otherwise healthy bodies in the name of functional or aesthetic normality. These stories demonstrate over and over again how easily biomedical research and practice can mask atrocity with benevolence and injustice with progress. Which leads me to ask: What, precisely, are we editing for?

Although muscle-eye-brain disease does not result from a single genetic variant, researchers agree that a single gene, named POMGNT1, plays a large role. Perhaps scientists will soon find a way to correct mutations in that and related genes. Perhaps people will no longer be born with it. But that means there would never be someone like Jason. Those prayers I mentioned above? Science will have retroactively answered them. That thought brings me to tears.

I wish we could cure cancer, relieve undue pain and heal each break and bruise. But I also wish for a world with Jason and people like him in it. I want a world accessible and habitable for people full stop not just the people we design. I worry that in our haste to make people healthy, we are in fact making people we want. We, who say we pray for healing, but in fact pray for others to be like us. We, who say were for reducing disease and promoting health, but support policies and practices aimed instead at being normal. We, who are often still unable to distinguish between positive, world-creating forms of disability and negative, world-destroying forms between Deafness, short stature or certain types of neurodiversity and chronic pain, Tay-Sachs or Alzheimers. It is with great responsibility that we as a society balance along the tightrope of biomedical progress. I long for us to find that balance. Ive certainly not found it for myself. Lest I forget how often weve lost it and how easy it is to fall, I hold dearly onto the living memory of Jason. I no longer pray for paradoxes, but for parity for the promise of a world engineered not for normality, but equality.

But that world will never come if we edit it away.

Read the original post:
Gene Editing Might Mean My Brother Would've Never Existed - TIME

Brain boost: Several regions across the brains of mice with a CHD8 mutation are larger (pink) than in controls.

Researchers have debuted two mouse models of autism made using the gene-editing tool CRISPR. Both strains lack one functional copy of CHD8, a gene with strong ties to autism1,2.

CRISPR allows researchers to quickly and efficiently insert specific mutations into single-cell mouse embryos. Several teams have used the method to make mouse models for other conditions, including Rett syndrome, an autism-related condition. The new mice represent the first use of the method to make models expressly for autism.

CHD8, a top autism candidate, was an obvious choice for this first foray: Almost all individuals with a harmful CHD8 mutation also have autism. They also have a characteristic syndrome that includes an enlarged head, gut problems and intellectual disability.

The two new strains of mice, along with three others made with conventional techniques, recapitulate some features seen in people with a CHD8 mutation. But they differ slightly from each other in their brain and behavioral features.

These variations may be due to differences in the mices genetic background, says Alex Nord, assistant professor of neuroscience at the University of California, Davis, who made one of the new CRISPR models.

Because the genetic background of people is also widely variable, the ability to make multiple mouse models of the same syndrome inexpensively is an advantage.

The continued accumulation of these data, models and reagents is going to be enormously important for the field, says Michael Talkowski, associate professor of neurology at Harvard University, who was not involved in making the mice.

Traditional methods for disabling a gene involve breeding mice for several generations in order to generate animals that carry the mutation in each of their cells. CRISPR, by contrast, allows researchers to alter the genome directly in a single-cell mouse embryo, speeding up the process and lowering costs substantially.

Since CRISPR/CAS9 has come out, making the mouse is no longer the longest part of the process, Nord says. CRISPR has shortened the timeline for engineering a mouse model from roughly two years to about six months, researchers say.

CRISPR also makes it possible to introduce mutations in mice that are otherwise genetically identical to controls. Researchers can tweak the gene in any way they like, inserting specific mutations rather than deleting genes. (Some studies have suggested that CRISPR can introduce unintended mutations, however.)

Nord and his colleagues made mice with a mutation that shuts down one copy of CHD8. The animals forget having seen an object before and fail to associate a location or sound with a shock features suggestive of memory and learning problems. They do not have social deficits or repetitive behaviors, both of which are hallmarks of autism. The researchers presented the mice at the 2016 International Meeting for Autism Research, and published their findings 26 June in Nature Neuroscience.

The brains of the Nord mice are larger than those of controls across several regions, including the cortex, hippocampus and amygdala. The mice with the biggest differences have the most trouble with learning and memory.

The researchers measured gene expression in brain tissue from the mice during gestation, at birth and in adulthood. They found hundreds of genes expressed at lower levels than in control mice. These include many genes that influence how genetic messages are spliced, or edited, into their final protein-coding sequences. Using a statistical model, the researchers concluded that splicing is altered in the mutant mice.

The researchers also tracked the expression of 141 genes associated with autism; they found 37 of these are expressed at unusually low levels in the mutant mice.

The other set of CHD8 mice made using CRISPR come from researchers at the Massachusetts Institute of Technology. These mice are just as likely as controls to approach and interact with another mouse. But unlike controls, they do not spend extra time with a mouse theyve never met before.

This could be a sign of social deficits, but it could also indicate a problem with memory, says co-lead investigator Guoping Feng, professor of brain and cognitive sciences.

The mice show no repetitive behaviors, but they show clear signs of anxiety, and avoid open spaces. They are also better than controls at learning how to balance on a rotating rod. This feature is seen in mice missing copies of other genes linked to autism, such as PTEN and NLGN3.

Overall, the findings in the Feng mice seem to match those in the Nord mice and most other CHD8 models, says Jill Silverman, assistant professor of psychiatry and behavioral sciences at the University of California, Davis. Silverman led the behavioral analysis of the Nord mice.

It was really reassuring, we saw all the same things as [the Feng team] with regards to autism-relevant behavior, Silverman says.

The Feng mice show atypical expression of genes that regulate the light-dark cycle and protein processing, among others. This is consistent with results in other CHD8 models, including the Nord mice.

Fengs team found that levels of genes involved in WNT signaling, a signaling pathway important for development, are significantly altered in the nucleus accumbens. This region, nestled deep in the brain, plays a role in sensing reward.

The researchers measured the strength of electrical currents in the nucleus accumbens in brain slices from the mutant mice, and found that excitatory signaling in the region is enhanced compared with controls. Dampening CHD8 levels specifically in the nucleus accumbens improves the mices motor learning, but not their anxiety. The study appeared 11 April in Cell Reports.

The findings implicate a reward brain region in autism, says Silverman. People with autism may not be finding social interactions as rewarding, so its a really interesting approach in that way, she says.

Feng and his team plan to use CRISPR to make mice that lack both copies of CHD8, but only in the brain. (Missing both copies throughout the body is lethal). This approach would enhance the mutations effects and make it easier to pin down CHD8s role in the brain, Feng says. His team also intends to make mice that carry each of the CHD8 mutations seen in people with autism.

Nord and his colleagues also plan to make mice with individual mutations linked to autism. These include a mutation in a genomic region that may control CHD8s expression. Because CRISPR mice are relatively inexpensive to make, Nord says, the researchers can take the risk that the mutation, and others like it, in fact do nothing.

Visit link:
Mice made with CRISPR usher in new era of autism research - Spectrum

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The CRISPR//Cas9 gene editing tool has quickly earned a reputation as a revolutionary technology, and its merits support the clout. This year has, in fact, seen so many CRISPR-related breakthroughs that its worthwhile to take a step back and take in all of the many accomplishments.

1. This week, circulating reports about the successful application of gene-editing human embryos in the US were confirmed by a research paper published in Nature. The researchers corrected one-cell embryo DNA to remove the MYBPC3 gene known to cause hypertrophic cardiomyopathy (HCM), a heart disease that affects 1 in 500 people.

2. This year, scientists successfully used gene editing to completely extract HIV from a living organism, with repeated success across three different animal models. In addition to the complete removal of the virus DNA, the team also prevented the progress of acute latent infection.

3. Semi-synthetic organisms were developed by breeding E.coli bacteria with an anomalous six-letter genetic code, instead of the normal four-base sequence. Additional gene editing was implemented to ensure that the new DNA molecules were not identified as an invasive presence.

4. The CRISPR method successfully targeted the command center of cancer called the hybrid fusion which leads to abnormal tumor growths. A cut-and-paste method allowed the creation of a cancer-annihilating gene that shrinks tumors in mice carrying human prostate and liver cancer cells.

5. Scientists also slowed the growth of cancerous cells, by targeting Tudor-SN, a key protein in cell division. Its expected that this technique could also slow the growth of fast-growing cells.

6. Gene editing techniques have also made superbugs kill themselves. By adding antibiotic resistant gene sequences into bacteriophage viruses, self-destructive mechanisms are triggered which protect bacteria.

7. Gene editing may even make mosquito-born diseases an extinct phenomenon. By hacking fertility genes, scientists have gained the ability to limit the spread of mosquitoes a success they credit to CRISPRs ability to make multiple genetic code changes simultaneously.

8. Using CRISPR, researchers have edited out Huntingtons disease from mice, pushing the symptomatic progression of the condition into reverse. Experts expect this promising technique to be applied to humans in the near future.

9. Outside of the medical field, CRISPR might also provide a more abundant and sustainable biofuel. By connecting several gene-editing tools, scientists engineered algae that produce twice the biofuel material as wild (or natural) counterparts.

Flickr: Sarah Fulcher

10. Very recently, the first-ever molecular recorder was developed a gene editing process that encodes a film directly into DNA code and with this ability, scientists embedded information into an E.coli genome.

11. Last but not least, and on the macro-scale, the U.S. Defense Advanced Research Projects Agency (DARPA) invested $65 million in a project called safe genes, designed to improve the accuracy and safety of CRISPR editing techniques. In addition to serving the public interest of avoiding accidental or intentional (cue ominous music) misuse, the seven research teams will remove engineered genes from environments to return them to baseline natural levels.

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11 Amazing Feats the Gene-Editing Tool CRISPR Just Made Possible - NBCNews.com

"Significant and Exciting"

This is a significant and exciting decision by the EPO, and we view this announcement as recognition of MilliporeSigma's important contributions to the genome-editing field, MilliporeSigma CEO Udit Batra, Ph.D., said. This patent provides protection for our CRISPR technology, which will give scientists the ability to advance treatment options for the toughest medical challenges we face today.

MilliporeSigma also predicted that it would be awarded patents for the technology in other countries as well.

The European patent to MilliporeSigma comes five months after the EPO announced an intention to grant a patent broadly covering CRISPR technology to Emmanuelle Charpentier, Ph.D., a director at the Max-Planck Institute in Berlin, together with the University of California (UC), and University of Vienna.

The patent consisted of broad claims directed to the CRISPR/Cas9 single-guide gene-editing system for uses in both noncellular and cellular settings, including in cells from vertebrate animals such as human or mammalian cellsas well as composition claims for use in any setting, including claims for use in a method of therapeutic treatment of a patient. The technology has been licensed to companies that include CRISPR Therapeuticswhose co-founders include Dr. Charpentierand ERS Genomics, both of which announced the EPO decision.

Dr. Charpentier, UC, and University of Vienna are in a legal battle royal with the Broad Institute of MIT and Harvard over who invented the gene-editing platform. Late last month, the European patent holders filed a brief with the U.S. Court of Appeals for the Federal Circuit seeking to reverse the February 15 decision by the Patent Trial and Appeal Board (PTAB). The PTAB found no interference in fact between 12 patents related to CRISPR technology that list as inventor Feng Zhang, Ph.D., of the Broad, and a patent application by Dr. Charpentier and Jennifer Doudna, Ph.D., of UC Berkeley.

The #CRISPR #patent situation in Europe just got a LOT more complicated, tweeted Jacob S. Sherkow, J.D., associate professor at the Innovation Center for Law and Technology, New York Law School, who has closely followed the CRISPR legal wrangle, on August 5.

Until now, he tweeted, the EPO granting of a patent to Dr. Charpentier, UC, and the University of Vienna didn't mean Zhang couldn't get his. Now, it's unclear.

Link:
MilliporeSigma to Be Granted European Patent for CRISPR Technology - Genetic Engineering & Biotechnology News

In BriefIn 2017, the hot new gene editing technique CRISPR has made unparalleled advancements in gene engineering. Here are 11 highlights.

The CRISPR//Cas9 gene editing tool has quickly earned a reputation as a revolutionary technology, and its merits support the clout. This year has, in fact, seen so many CRISPR-related breakthroughs that its worthwhile to take a step backand take in all of the many accomplishments.

1. This week, circulating reports about the successful application of gene-editing human embryos in the US were confirmed by a research paper published in Nature. The researchers corrected one-cell embryo DNA to remove the MYBPC3 gene known to cause hypertrophic cardiomyopathy (HCM), a heart disease that affects 1 in 500 people.

2. This year, scientists successfully used gene editing to completely extract HIV from a living organism, with repeated success across three different animal models. In addition to the complete removal of the virus DNA, the team also prevented the progress of acute latent infection.

3. Semi-synthetic organisms were developed by breeding E.coli bacteria with an anomalous six-letter genetic code, instead of the normal four-base sequence. Additional gene editing was implemented to ensure that the new DNA molecules were not identified as an invasive presence.

4. The CRISPR method successfully targeted the command center of cancer called the hybrid fusion which leads to abnormal tumor growths. A cut-and-paste method allowed the creation of a cancer-annihilating gene that shrinks tumors in mice carrying human prostate and liver cancer cells.

5. Scientists also slowed the growth of cancerous cells, by targeting Tudor-SN, a key protein in cell division. Its expected that this technique could also slow the growth of fast-growing cells.

6. Gene editing techniques have also made superbugs kill themselves. By adding antibiotic resistant gene sequences into bacteriophage viruses, self-destructive mechanisms are triggered which protect bacteria.

7. Gene editing may even make mosquito-born diseases an extinct phenomenon. By hacking fertility genes, scientists have gained the ability to limit the spread of mosquitoes a success they credit to CRISPRs ability to make multiple genetic code changes simultaneously.

8. Using CRISPR, researchers have edited out Huntingtons disease from mice, pushing the symptomatic progression of the condition into reverse. Experts expect this promising technique to be applied to humans in the near future.

9. Outside of the medical field, CRISPR might also provide a more abundant and sustainable biofuel. By connecting several gene-editing tools, scientists engineered algae that produce twice the biofuel material as wild (or natural) counterparts.

10. Very recently, the first-ever molecular recorder was developed a gene editing process that encodes a film directly into DNA code and with this ability, scientists embedded information into an E.coli genome.

11. Last but not least, and on the macro-scale, the US Defense Advanced Research Projects Agency (DARPA) invested $65 million in a project called safe genes, designed to improve the accuracy and safety of CRISPR editing techniques. In addition to serving the public interest of avoiding accidental or intentional (cue ominous music) misuse, the seven research teams will remove engineered genes from environmentsto return them to baselinenatural levels.

Original post:
11 Incredible Things CRISPR Has Helped Us Achieve in 2017 - Futurism

The Potential of CRISPR

The potential of the gene editing toolCRISPRjust seems to keep growing and growing, and the latest experimental use of the technology is creating skin grafts that trigger the release of insulin and help manage diabetes.

Researchers have successfully tested the idea with mice that gained less weight and showed a reversed resistance to insulin because of the grafts (high insulin resistance is a common precursor to type 2 diabetes).

In fact, the team from the University of Chicago says the same approach could eventually be used to treat a variety of metabolic and genetic conditions, not just diabetes its a question of using skin cells to trigger different chemical reactions in the body.

We didnt cure diabetes, but it does provide a potential long-term and safe approach of using skin epidermal stem cells to help people with diabetes and obesity better maintain their glucose levels,says one of the researchers, Xiaoyang Wu.

If youre new to theCRISPR(Clustered Regularly Interspaced Short Palindromic Repeats) phenomenon, its a new and innovative way of editing specific genes in the body, using a biological copy and paste technique: it can doeverything fromcut out HIV virus DNA to slow thegrowth of cancer cells.

For this study, researchers used CRISPR to alter the gene responsible for encoding a hormone calledglucagon-like peptide-1(GLP-1), which triggers the release of insulin and then helps remove excess glucose from the blood.

Type 2 diabetescomes about due to a lack of insulin, also known as insulin resistance.

Using CRISPR, the GLP-1 gene could be tweaked to make its effects last longer than normal. The result was developed into skin grafts that were then applied to mice.

Around 80 percent of the grafts successfully released the edited hormone into the blood, regulating blood glucose levels over four months, as well as reversing insulin resistance and weight gain related to a high-fat diet.

Significantly, its the first time the skin graft approach has worked for mice not specially designed in the lab.

This paper is exciting for us because it is the first time we show engineered skin grafts can survive long term in wild-type mice, and we expect that in the near future this approach can be used as a safe option for the treatment of human patients,says Wu.

Human treatments will take time to develop but the good news is that scientists are today able to grow skin tissue very easily in the lab using stem cells, so that wont be an issue.

If we can make it safe, and patients are happy with the procedure, then the researchers say it could be extended to treat something likehaemophilia, where the body is unable to make blood clots properly.

Any kind of disease where the body is deficient in specific molecules could potentially be targeted by this new technique. And if it works with diabetes, it could be time to say goodbye to needles and insulin injections.

Other scientists who werent directly involved in the research, including Timothy Kieffer from the University of British Columbia in Canada, seem optimistic.

I do predict that gene and cell therapies will ultimately replace repeated injections for the treatment of chronic diseases, Kieffer told Rachel Baxter atNew Scientist.

The findings have been published inCell Stem Cell.

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CRISPR Skin Grafts Could Replace Insulin Shots For Diabetes - Futurism

Existing cancer immunotherapies harness T cells that recognize and home in on tumor-specific targets and kill the cancer cells. Immunotherapy using checkpoint inhibitors, for example, disconnects immune system restraints so that the T cells can attack the cancer cells. Other forms of immunotherapy, including cancer vaccines and adoptive T-cell therapy, increase the numbers of cytotoxic T cells that are mobilized to the tumor.

Immunotherapy can be highly effective against advanced cancers in some patients, but in other cases treatment doesnt work. To try to understand the genetic basis of these differing responses, scientists at the U.S. National Institutes of Health developed a genome-scale CRISPR/Cas9 screen that allowed them to knock out every single gene in a melanoma cell line and then systematically test each gene for its effect on T-cell responses against the melanoma. Using this "two-cell type" (2CT)-CRISPR assay, the researchers, led by Shashank Patel, Ph.D., and Nicholas Restifo, M.D., who is a senior investigator with NCI's Center for Cancer Research, identified more than 100 "essential" genes that were required in the melanoma line for T cells to effectively engage with and kill the cells. When these genes were knocked out, the tumor cells were more able to resist exposure to T cells that had been engineered specifically to recognize tumor-associated antigens.

The researchers published their studies in the August 7 issue of Nature, in a paper entitled "Identification of Essential Genes for Cancer Immunotherapy. The NIH team worked in close collaboration with Feng Zhang, Ph.D., from MIT, one of the original innovators of the CRISPR technology. Neville Sanjana, Ph.D., from the New York Genome Center and New York University was co-first author of the study.

CRISPR/Cas9 screens have previously been used to identify genes that play key roles in cancer cell proliferation, drug resistance, and metastasis, the authors point out. To identify which genes in tumors are requisite for the "effector function of T cells," the team developed the 2CT-CRISPR assay, consisting of human T cells as effectors and melanoma cells as targets, to evaluate the effects of individual gene knockouts on cancer cell susceptibility to T-cell killing. Many of the hundred or so genes identified were directly involved in cytokine release, or in antigen processing and presentation, but dozens of the genes identified were not known to be required for cytotoxic T-cell-based immunotherapy.

This indicated that the loss of genes that T cells need to kill cancer cells might be at least partially responsible for why immunotherapy fails in some patients, Dr. Restifo suggested to GEN. However, we were really surprised to find dozens of tumor genes that had major impacts on tumor cell survival, which hadnt previously been linked with the ability of T cells to kill target cancer cells. Exploring potentially new signaling pathways mediated by these genes could help us to understand how T cells interact with cancer cells to bring about cell death, and how cancers can evade the immune system.

With their list of the 100 most necessary tumor genes in hand, the researchers looked at the gene expression profiles of nearly 11,500 human tumors from The Cancer Genome Atlas (TCGA) database, across 36 tumor types, to see whether loss of these tumor genes associated with decreased cytolytic activity. The analysis identified a set of 19 genes that correlated with cytolytic activity across most of the cancer types. Ten of these were inducible by interferon- (IFN), which indicated that they might be upregulated in cancers because of increased T-cell mobilization. Loss of expression of these 19 genes within tumors could diminish or extinguish the presentation of tumor antigens (including HLA-A, HLA-F, B2M, TAP1 and TAP2); T-cell co-stimulation (ICAM1, CLECL1, LILRA1 and LILRA3); or cytokine production and signaling (JAK2 and STAT1) in the tumor microenvironment that drive infiltration and activation of T cells, and thus serve as a principal mechanism in immune evasion, the researchers write in their published paper.

The team next focused on one gene, APLNR, which codes for the apelin receptor, a G protein-coupled receptor (GPCR) that hadnt previously been associated with T-cell killing of cancer, but which is known to be mutated in a number of different tumor types. They identified seven different mutations in this gene in the genetic makeup of metastatic melanoma and lung cancer patients who had failed therapy using immune checkpoint inhibitors.

When the team introduced these same mutations into a melanoma cell line, the cancer cells were more resistant to T-cell attack. And when they injected engineered melanoma cells that lacked the APLNR gene into experimental mice, the resulting tumors were resistant to checkpoint inhibitor therapy and didnt respond as well to adoptive cell transfer as tumors with a normal APLNR gene. Dr. Patel concluded that these data demonstrate that APLNR loss reduces the effectiveness of T-cell-based cancer therapies, including immune checkpoint blockade and ACT.

More work will be needed to validate the relevance of all the genes identified by the studies, Dr. Restifo stressed to GEN. We hope that this comprehensive list of genes will act as a blueprint for further study so that we can better understand tumor resistance to cancer therapies that hinge on T-cell attack. Looking at mutations in these genes in individual patients who failed immunotherapy may enable physicians to devise the most appropriate treatments for each individual patient, according to their essential gene profiles. More importantly, we are working toward developing new approaches to cancer therapy that help more patients with cancer.

The study findings also indicate that the success of cancer immunotherapy depends on the interplay between a far greater number of genes than previously thought, Dr. Restifo commented. A deeper understanding of how T cells interact with potential target cells could also help us to develop more effective treatments for infectious and autoimmune diseases.

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CRISPR Screen Identifies Top 100 Essential Genes for Cancer ... - Genetic Engineering & Biotechnology News