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News Article | February 21, 2017
Site: www.eurekalert.org

Scientists from the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, have identified novel mutations in bacteria that promote the evolution of high-level antibiotic resistance. The findings, published in eLife, add to our understanding of how antibiotic resistance develops, which the team says is crucial for maintaining the effectiveness of both existing and future drugs. The rise of antibiotic-resistant bacteria is challenging clinicians, with some infections already resistant to nearly all available drugs. A 2013 report from the Centers for Disease Control and Prevention estimates that such infections kill at least 23,000 people each year in the United States alone*. Deborah Hung, senior author of the current study and Core Institute Member and Co-Director of the Infectious Disease and Microbiome Program at the Broad Institute, says: "Some species of bacteria, including mycobacteria, develop drug resistance as a result of mutations in their genes. We wanted to gain new insight into the molecular processes that promote resistance in these species by looking at the relationships between the concentration of antibiotics, their killing effects on bacteria, and the emergence of drug-resistant mutants." To do this, Hung and her team grew hundreds of cultures of the species Mycobacterium smegmatis (M. smegmatis), a cousin of the bacterium that causes tuberculosis. They exposed the bacteria to low antibiotic concentrations, where the drugs' microbe-killing effects were relatively slow. This allowed the team to monitor the killing of sensitive bacteria while isolating individual wells where mutants developed. "We detected the outgrowth of drug-resistant mutants in a fraction of our cultures," says first author James Gomez. "Each individual carried single mutations in different components of the ribosome, the complex molecular machine responsible for building proteins within cells." The team found that these novel ribosomal mutations granted the bacteria resistance to several different classes of antibiotics that do not even target the ribosome, and to which the mutants had never been exposed. They also enhanced resistance to two non-antibiotic stresses: heat shock and membrane stress. Gomez explains: "We did see a fitness cost to the bacteria in that the mutations reduced their growth rate. However, the reprogramming that occurred within the cells in response to the mutations made the bacteria much less sensitive to both antibiotic and non-antibiotic stresses. This suggests that, in species such as M. smegmatis, these types of mutations can enhance fitness in multidrug environments and serve as stepping stones toward the development of high-level drug resistance, despite the cost that the mutations have on growth." The team now wants to explore this phenomenon across diverse bacterial species, including Mycobacterium tuberculosis, by coupling experimental biological approaches with a thorough exploration of genome sequence information. A more complete understanding of how multidrug resistance emerges could help in the development or optimisation of new drugs for treating bacterial infections. The paper 'Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment' can be freely accessed online at http://dx. . Contents, including text, figures, and data, are free to reuse under a CC BY 4.0 license. *CDC. Antibiotic Resistance Threats in the United States, 2013. Centers for Disease Control and Prevention, 2013: https:/ eLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine -- from basic biological research to applied, translational, and clinical studies. All papers are selected by active scientists in the research community. Decisions and responses are agreed by the reviewers and consolidated by the Reviewing Editor into a single, clear set of instructions for authors, removing the need for laborious cycles of revision and allowing authors to publish their findings quickly. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org.


News Article | February 14, 2017
Site: www.sciencemag.org

Editing the DNA of a human embryo to prevent a disease in a baby could be ethically allowable one day—but only in rare circumstances and with safeguards in place, says a widely anticipated report released today. The report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concludes that such a clinical trial “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child, says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison. Some researchers are pleased with the report, saying it is consistent with previous conclusions that safely altering the DNA of human eggs, sperm, or early embryos—known as germline editing—to create a baby could be possible eventually. “They have closed the door to the vast majority of germline applications and left it open for a very small, well-defined subset. That’s not unreasonable in my opinion,” says genome researcher Eric Lander of the Broad Institute in Cambridge, Massachusetts. Lander was among the organizers of an international summit at NAS in December 2015 who called for more discussion before proceeding with embryo editing. But others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,” says Edward Lanphier, CEO of the DNA editing company Sangamo Therapeutics in Richmond, California. Two years ago, he co-authored a commentary calling for a moratorium on clinical embryo editing. One advocacy group opposed to embryo editing goes further. “We’re very disappointed with the report. It’s really a pretty dramatic shift from the existing and widespread agreement globally that human germline editing should be prohibited,” says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California. Modifying human DNA in ways that could be passed on to future generations has long been considered ethically off limits and is banned in many countries. But new DNA editing tools, such as CRISPR, that make genome modifications much easier have revived the discussion. In April 2015, researchers in China reported that they had used CRISPR, with limited success, to repair a disease-causing gene in human embryos. Although the researchers used defective embryos and had no intention of implanting them in a woman’s uterus, the work sparked fears that designer babies were around the corner. The controversy led to the 2015 NAS summit, where organizers concluded that “it would be irresponsible to proceed with any clinical use of germline editing” without more research on safety and societal discussion. The science and medicine acadmies then formed an international committee to look more closely at the science and ethical issues. The committee’s report finds that human embryo editing may be acceptable to prevent a baby from inheriting a serious genetic disease—but only if specific safety and ethical criteria are met. For example, the couple cannot have “reasonable alternatives,” such as the option of selecting healthy embryos for in vitro fertilization (IVF) or using prenatal testing and aborting a fetus with the disease. One situation that could meet the report’s criteria would be if both parents have the same disease, such as cystic fibrosis, that is caused by carrying two copies of a mutation, the report says. In that case, an embryo will also carry the harmful mutations. Still, the panel says that strict government oversight should be in place to prevent anyone from using germline editing for other purposes, such as to give a baby desirable traits. “They want to put friction tape on the slope so the slope isn't slippery,” Lander says. Biologist David Baltimore of the California Institute of Technology in Pasadena, who chaired the organizers of the 2015 NAS summit, says the report’s recommendations essentially codify what the summit committee concluded based on the views of researchers and others. The report’s authors are “in a not very different position than we were in,” except that the report explicitly spells out criteria for allowing an embryo editing trial. But Darnovsky says the report “opens the door” to embryo editing. She is concerned that once regulators have approved an embryo editing treatment for a serious disease, IVF clinics will feel free to use it to select embryos with desirable traits. She disagrees with a suggestion in the report that the criteria are so stringent that they could “have the effect of preventing all clinical trials involving germline genome editing.” The report itself acknowledges that the criteria are “necessarily vague” and open to interpretation. Like other bodies that have recently reviewed CRISPR and older genome editing methods, the committee also endorsed basic research using embryo editing to study areas such as early human development. The United Kingdom and Sweden have both approved such experiments, which do not involve implanting embryos with the aim of producing a baby. Currently, such experiments cannot be done with federal funding in the United States because of a congressional prohibition on using taxpayer funds for research that destroys human embryos. Congress has also banned the U.S. Food and Drug Administration from considering a clinical trial of embryo editing. As for gene editing in patients’ cells that aren’t inherited, clinical trials are already underway for HIV, hemophilia, and leukemia. The committee found that existing regulatory systems for gene therapy are sufficient for overseeing such work. Genome editing should “not proceed at this time” for enhancement, such as to increase a healthy person’s muscle strength or lower their cholesterol levels, the panel said. However, it said discussions should continue. The academies are helping to organize another international summit in China later this year to further discuss the issues.


News Article | February 15, 2017
Site: cen.acs.org

University of California, Berkeley, scientists have found entirely new classes of Cas proteins, the enzymes responsible for snipping DNA in the CRISPR gene-editing system. The discovery expands the ever-growing CRISPR toolbox and creates a new wrinkle in the ongoing patent dispute between Berkeley and the Broad Institute of Harvard University and MIT over the gene-editing technology. Jillian F. Banfield led the Berkeley team, which scoured 155 million genes from microbes that cannot be grown in labs to find the Cas proteins. These microbes live in places as varied as groundwater, acidic drainage from mines, and the intestines of infants. In addition to finding new versions of traditional Cas9 proteins, the researchers discovered entirely new classes of Cas enzymes, dubbed CasX and CasY (Nature 2016, DOI: 10.1038/nature21059). Because Cas proteins are large, it’s challenging to deliver them into cells for gene-editing purposes. The newly discovered CasX enzymes, however, are among the smallest Cas proteins known, potentially a key advantage over other Cas variants, including the Cas9 class of protein that’s used by almost everyone working with CRISPR today. Cas9 is part of microbial immune systems found in the pathogenic Streptococcus pyogenes and many other species. “There is just an incredible diversity of microbial life out there,” Banfield says. And the CasX and CasY discovery “is a beautiful example of the kinds of valuable things that can be found.” Banfield partnered with Jennifer A. Doudna’s lab at UC Berkeley to demonstrate CasX and CasY’s potential for gene-editing in bacterial cells. Doudna, a cocreator of the CRISPR/Cas tool along with Max Planck Institute for Infection Biology’s Emmanuelle M. Charpentier, is currently embroiled in a patent dispute with the Broad Institute over who holds the licenses to CRISPR systems that use Cas9. The Berkeley researchers recently filed a patent application related to the newly reported CasX and CasY enzymes. Because these variants are different enough from Cas9, they could give Doudna and colleagues a cushion if they lose the ongoing patent fight. The timing of the Berkeley team’s Nature report on CasX and CasY is impeccable. The week before it was published, several companies, including CRISPR Therapeutics, Intellia Therapeutics, and Caribou Biosciences—which are all tied to either Doudna or Charpentier—formalized an alliance to share, protect, and enforce their intellectual property. The Broad-associated Editas Medicine quickly retaliated and announced its own agreement with five universities, licensing “advanced forms of Cas9,” as well as a previously reported Cas9 alternative enzyme named Cpf1. Jacob S. Sherkow of New York Law School says that in retrospect, knowledge of CasX and CasY likely fueled the cross-licensing agreements. “That is the piece of the jigsaw puzzle we were missing” when the deals took place, Sherkow says. “It cannot be coincidence.” “It is possible that all of the companies involved in CRISPR technologies could avoid being ‘losers’ in the patent dispute by just using different versions” of Cas proteins, says Knut J. Egelie of the Norwegian University of Science & Technology. Alternatives to Cas9 “will level out the game and make the patent interference decision less important,” he adds. Banfield says her lab will continue exploring the mysterious genomes of difficult-to-cultivate microbes, while Doudna’s group will carry out gene-editing tests with the new enzymes in cells beyond bacteria. This article has been translated into Spanish by Divulgame.org and can be found here.


News Article | February 15, 2017
Site: www.sciencemag.org

The U.S. Patent Trial and Appeal Board ruled today in favor of the Broad Institute in Cambridge, Massachusetts, in the initial legal step of a high stakes battle over who will control the valuable intellectual property linked to CRISPR, the powerful genome-editing tool. The decision may be appealed by the University of California (UC), however, which last year requested the “interference” from the patent board because it contends that a team of scientists it represented invented the technology and that the Broad researchers piggybacked on their discovery. The patent board decision declared “Broad has persuaded us that the parties claim patentably distinct subject matter, rebutting the presumption created by declaration of this interference." Jacob Sherkow, an intellectual property attorney at the New York Law School in New York City, says the decision could be “a decisive knock out for the Broad.” He says he now expects UC to take the case to the U.S. Court of Appeals for the Federal Circuit. Jennifer Doudna, a UC Berkeley structural biologist, also still has a patent pending for the CRISPR invention. UC in May 2012 filed a patent for Doudna, Emmanuelle Charpentier (then of Umeå University in Sweden), and their colleagues for their discovery that CRISPR, an immune system used by bacteria, could serve as a genome-editing tool in any type of cell. But the Doudna/Charpentier team, as they reported in a landmark paper published online by on 28 June 2012, at that point had only used CRISPR to cut DNA in test tube studies. In contrast, a team led by the Broad’s Feng Zhang reported in the 3 January 2013 online edition of that it had used CRISPR to cut DNA in human cells, opening the door for the tool to be used in medicine. Broad beginning in December 2012 filed a dozen patents based on the eukaryotic use of CRISPR, and paid the U.S. Patent and Trademark Office (USPTO) to do a fast-track review. The first of those patents issued in April 2014, stunning many researchers in the CRISPR field—and some of the companies that had formed around the promising new technology. In a teleconference for the media held by UC, Doudna stressed that today's interference decision means USTPO will now move forward on her patent application and that it “likely” will issue, potentially forcing companies that want to use CRISPR to pay licensing fees to both Broad and UC. “They have a patent on green tennis balls. We [likely] will have a patent on all tennis balls,” says Doudna. “I don’t think it really makes sense.” Lynn Pasahow, an attorney with Fenwick & West in Mountain View, California, who represented the UC in the case said no decision has yet been made about whether there will be an appeal. “At this point we are studying the opinion that came out this morning and the university is considering all of its options,” says Pasahow. When asked whether UC would now seek to cut a deal with the Broad—which was attempted at the start of the interference—Pasahow said “there’s no requirement that the two parties work out a settlement.” Dana Carroll, a biochemist at the University of Utah in Salt Lake City who specializes in ways to cut DNA, testified on behalf of UC in the patent interference, contending that applying the Doudna/Charpentier team’s discovery to human cells was “obvious”—indeed, Doudna’s group published a paper showing that CRISPR could edit eukaryotic cells a few weeks after Zhang published his team’s study. The patent board did not agree, however. “One of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment,” it wrote. “I am disappointed that the Patent Office did not agree with what I saw as a clear and compelling perspective on the case,” Carroll says. Broad issued a statement that says the competing patents “are about different subjects and do not interfere with each other.” The statement says Broad has “deep respect” for the contributions made by Doudna and Charpentier, who have already won many prestigious awards for their work. It also notes that USPTO now has issued 50 patents related to CRISPR—14 have gone to Broad—and predicts many more will be issued.


News Article | February 23, 2017
Site: www.biosciencetechnology.com

Last week, the U.S. Patent Trial and Appeal Board issued an important decision in a dispute over intellectual property rights to the powerful gene-editing system known as CRISPR. Using this system, researchers can make changes to a cell’s genome more easily and with greater precision than they can with other approaches. The method has great potential to advance our understanding of the biology and treatment of human disease. The Broad Institute and MIT hold several foundational CRISPR-related patents based on research led by Feng Zhang, who is the James and Patricia Poitras Professor in Neuroscience at the McGovern Institute for Brain Research at MIT and a core member of the Broad Institute. Zhang is also an associate professor in MIT’s Department of Brain and Cognitive Sciences with a joint appointment in the Department of Biological Engineering. The University of California at Berkeley has also filed CRISPR-based patent applications, stemming from research led by by Jennifer Doudna of UC Berkeley and Emmanuelle Charpentier, who is currently the director of the Max Planck Institute for Infection Biology in Berlin. UC Berkeley and Charpentier asked the U.S. Patent Trial and Appeal Board to declare a “patent interference” to determine who was the first to invent key CRISPR inventions, suggesting that certain claims identified by UC Berkeley in its application were to the same invention as the claims in the Broad Institute’s patents. The Board’s Feb. 15 decision means that the Zhang patents will remain in place, although UC Berkeley is weighing its options, including the possibility of an appeal to the Federal Circuit. MIT News talked with Charles Jennings, director of the McGovern Institute Neurotechnology Program, who also oversees communcations at the Institute, to learn more about the decision and its implication for gene-editing research. Q: What is CRISPR, and what research is being done at MIT and the Broad Institute? A: CRISPR is a naturally occurring system by which bacteria and other microorganisms fight viral infections. CRISPR systems, such as CRISPR-Cas9 and CRISPR-Cpf1, have been harnessed as powerful and efficient tools for genome editing, with far-reaching implications for biology and medicine. Feng Zhang, a leading pioneer in this work, and his group submitted a paper reporting genome editing in mammalian cells (including human and mouse cells), using two different CRISPR-Cas9 systems from different bacterial species to target multiple genes in the cells’ genomes. This paper, which appeared in Science on Jan. 3, 2013 (Cong et al., 2013) is now the most cited paper in the genome-editing field. Since initiating this work, which began in early 2011 soon after Zhang started as a new assistant professor, his group has continued to develop the CRISPR-Cas9 system for genome editing in eukaryotic cells. The researchers have also explored the natural diversity of CRISPR systems, which allowed them to discover new systems with advantageous properties distinct from those of CRISPR-Cas9. Many other groups at MIT (along with thousands of other labs worldwide) are now using Zhang’s CRISPR-related tools, which he has made widely available for academic research via the Addgene website, where they have been requested more than 37,000 times. Q: What did the U.S. Patent and Trademark Office rule on Feb. 15? A: Zhang and his colleagues have been awarded more than 13 patents for their CRISPR-related work, which is focused primarily on the use of CRISPR in eukaryotic cells. After the first of Zhang’s patents were awarded, UC Berkeley suggested a patent proceeding known as an interference be declared, arguing that Zhang’s invention was the same as their pending claims. On Feb. 15, the Patent Trial and Appeal Board (which is part of the U.S. Patent and Trademark Office) granted Broad's motion for no-interference-in-fact, rejecting UC Berkeley's arguments. MIT welcomes this decision, which confirms that the patents and applications of the Broad Institute and MIT for use of CRISPR in eukaryotic cells are patentably distinct from the biochemical experiments in test tubes in the UC Berkeley filing. The Patent Trial and Appeal Board (PTAB) confirmed that Zhang’s work, which began in 2011, represents a new invention that was not obvious from the prior work of Doudna, Charpentier, and colleagues, which was confined to results in a test tube. Specifically, in the words of the PTAB decision, “one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment.” Q: How will this decision influence gene-editing research moving forward? A: The Broad Institute and MIT are committed to making the CRISPR technology widely available for both academic and commercial use, including human therapeutic applications. The Broad Institute, which manages Feng Zhang’s CRISPR-related intellectual property (IP) on behalf of both institutions, has developed what we have termed an “inclusive innovation” model for licensing CRISPR-related IP, in order to maximize the public benefit of this groundbreaking technology. The PTAB decision of Feb. 15 does not alter our policy, and we expect that genome-editing research will continue to move forward rapidly, with potentially transformative benefits for many fields including basic and disease-related research, agriculture, and medicine.


News Article | February 16, 2017
Site: www.biosciencetechnology.com

In a highly anticipated decision that could sway the fortunes of a handful of biotechnology companies, the federal patent office has turned back a challenge to patents covering a widely used method for editing genes. The office's board of appeals ruled Wednesday that the Broad Institute of MIT and Harvard can keep patents it had been awarded for a technique called CRISPR that lets scientists alter DNA within cells. It turned back a challenge from the University of California, Berkeley. The school had filed its own CRISPR patent application in 2012 a few months before the Broad institute, but the Broad got its patents approved while Berkeley's application is pending. The financial implications are huge, since CRISPR may lead to many lucrative products in medicine, agriculture and elsewhere. One company that has licensed Broad's technology, Editas Medicine Inc., saw its shares jump by 29 percent Wednesday. In a statement, Berkeley said it respects the ruling, but that it will "carefully consider all options for possible next steps in this legal process, including the possibility of an appeal." The patent dispute involved work led by Feng Zhang of the Broad Institute and Jennifer Doudna and Emmanuelle Charpentier at Berkeley. Lawyers for Berkeley maintained that Doudna and Charpentier were the first to invent CRISPR for use in all settings. They said the work at Broad, which showed how to use CRISPR in the relatively complex cells of plants, people and other animals, wasn't enough of an advance beyond the Berkeley work to warrant its own patents. The appeals board, however, concluded that the Broad work was not simply an obvious extension of the research described in the Berkeley patent application. So Broad's patent coverage is different from Berkeley's, the board ruled. Jacob Sherkow, who specializes in patent law for matters of biological sciences at the New York Law School, said he thinks it would be worthwhile for Berkeley to take the matter to a federal appeals court.


News Article | February 16, 2017
Site: www.npr.org

The U.S. patent office has delivered a potentially lucrative victory to bioengineer Feng Zhang of the Broad Institute in Massachusetts, regarding patents for an extraordinarily useful gene-editing tool. CRISPR, a technology that's already worth billions of dollars, is shaping up to play a big role in medicine and medical research because it can edit DNA with unprecedented accuracy. But exactly who has the right to profit from the technology has been up for debate. Wednesday the U.S. Patent and Trademark Office said patents issued to the Broad Institute in 2014, and then challenged by the University of California, Berkeley, are in fact valid. "It's a pretty monumental decision here," said Jacob Sherkow, an associate professor at the New York Law School, who has been tracking the dispute closely. "It seems to reward the most valuable aspect of CRISPR to the Broad Institute," Sherkow told Shots. The proceedings aren't entirely settled, but as Sherkow sees the situation, the Broad Institute — a joint venture of Harvard University and MIT — will hold the patent for using CRISPR in human beings, other animals, and plants. Sherkow told Shots he believes Cal's patent, which has not yet been issued, could be limited to bacteria. "Obviously the patents covering the application of this technology in human cells ... are going to be much more financially valuable than using the same technology in bacteria," Sherkow says, "because one can develop drugs and other therapies from them." Investors Wednesday seemed to agree with this assessment. The value of companies that were spun off to license the Broad patents rose sharply, while the company based on the Berkeley patent lost value. Potentially, tens of billions of dollars are at stake here, both for the companies and for the universities. Biochemist Jennifer Doudna, of U.C. Berkeley and the Howard Hughes Medical Institute, discovered the biology that underlies this technology along with a European colleague, Emmanuelle Charpentier, who is now director of the Institute for Infection Biology at the Max Planck Institute in Berlin. Doudna told Shots she isn't convinced that Berkeley is the big loser here. She said the ruling paves the way for her patent application to move forward. "We're looking forward to having our patent issued," she said. "And our patent is a very broad patent that covers the composition and the use of this technology in all cell types." If the patent office rules the way Doudna hopes it will, people wanting to use CRISPR in higher organisms will have get licenses from both Berkeley and the Broad Institute. "That's the thing that I think is a bit crazy about the way the decision comes down," Doudna said. "It leaves the field — the situation — where a license would be necessary from both parties. There's not further clarity at this stage." There's yet another possibility: Berkeley could appeal Wednesday's ruling, and once again challenge the Broad Institute's patents. Doudna said the university hasn't decided what to do just yet.


News Article | February 24, 2017
Site: phys.org

Facing off are the top international experts in the fast-growing field of gene-editing—pitting an American of Chinese origin, Feng Zhang, against the French-American duo of Emmanuelle Charpentier and Jennifer Doudna. The US Patent and Trademark Office ruled last Wednesday in favor of Zhang, who is a researcher at the Broad Institute, a collaboration between Harvard University and the Massachusetts Institute of Technology. After that decision, which stunned many scientific observers, Editas Medicine, a start-up linked to Broad, saw its stock soar. Meanwhile, shares plummeted for companies that believed the patent rights would go to Charpentier and Doudna. The dispute mingles science and economics, with billions of dollars in contracts hanging in the balance. Charpentier and Doudna "would be crazy not to appeal. The cost-benefit ratio demands it," said Jorge Contreras, an expert in genetics and intellectual property at the University of Utah. Charpentier, who is affiliated with the Max Planck Institute of Berlin, and Doudna of the University of California, Berkeley, have already won a $3 million US Breakthrough Prize for their work and are widely believed to be in line for a Nobel Prize someday. They developed a tool called CRISPR-Cas9, which experts say is revolutionizing the field of genetics the way word processors did for typewriters. Their discovery, published in the prestigious journal Science in June 2012, sent shockwaves through scientific community. Much like a surgical scalpel, the technique allows the genome to be edited by clipping out a specific area of DNA and in some cases replacing it with new instructions. The breakthrough has opened up countless possibilities in the fields of health and agriculture. The French-American team filed for a patent in May 2012, describing how they used CRISPR with a simple type of bacteria. Zhang applied CRISPR to cells with a nucleus, known as eukaryotes, an innovation that had the potential to broaden genetic editing to human cells. He published his research months after Charpentier and Doudna. Zhang also applied for a patent—following a fast-track procedure that was more costly than the route taken by Doudna and Charpentier—and won. Enter the legal battle, as UC Berkeley and the Broad Institute face off over the patent rights to a technology that has aroused both vast hopes and deep ethical concerns about its potential to forever alter species and ecosystems. After a hearing in December, the US Patent Trial and Appeal Board of the USPTO announced last Wednesday that the patent application by the Broad Institute caused no "interference" with the larger patent request by Berkeley, and Charpentier and Doudna. But the two women have not conceded defeat. Their Broad patent is "sufficiently distinct as to be separately patentable from the claims of the Doudna/Charpentier group's patent application, which cover the use of CRISPR-Cas9 in any setting, including eukaryotic cells and other cell types," said a statement from UC Berkeley. Doudna used a sports metaphor to put Zhang's victory in context with what her group intends to seek. "They have a patent on green tennis balls; we will have a patent on all tennis balls," she told a press conference. Experts say that this outcome is a plausible one. "It is entirely possible that Berkeley will get broad claims covering all uses of CRISPR, while Broad's are limited to eukaryotes," said Contreras. "Thus, anyone wishing to use CRISPR (e.g., including agro uses), will need a license from Berkeley, while only uses involving eukaryotes will require both Berkeley and Broad." But Jacob Sherkow, an associate professor of law at the New York Law School, said in his view, Broad has obtained rights to the technology that are potentially very profitable and would exclude other competitors from the field when it comes to using CRISPR. Even if Berkeley did manage to receive broader rights to CRISPR, "the patent would be weak and wouldn't likely stand up to later challenges in court," he told AFP.


Li H.,Broad Institute | Homer N.,University of California at Los Angeles
Briefings in Bioinformatics | Year: 2010

Rapidly evolving sequencing technologies produce data on an unparalleled scale. A central challenge to the analysis of this data is sequence alignment, whereby sequence reads must be compared to a reference. A wide variety of alignment algorithms and software have been subsequently developed over the past two years. In this article, we will systematically review the current development of these algorithms and introduce their practical applications on different types of experimental data. We come to the conclusion that short-read alignment is no longer the bottleneck of data analyses. We also consider future development of alignment algorithms with respect to emerging long sequence reads and the prospect of cloud computing. © The Author 2010. Published by Oxford University Press.


Patent
Novartis, Broad Institute and Dana-Farber Cancer Institute | Date: 2013-06-26

The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Cyclin Dependent kinase inhibitors (CDKi), methods of determining the sensitivity of a cell to a CDKi, methods of treating a patient with a CDKi and methods of screening for candidate CDKi.

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