Research Area: Genome Engineering

​CRISPR, SHERLOCK, REPAIR, RNA editing, DNA editing, brain disorders, diagnostics, disease models, therapeutics

Feng Zhang elected to National Academy of Sciences

Anne Trafton |

Feng Zhang has been elected to join the National Academy of Sciences (NAS), a prestigious, non-profit society of distinguished scholars that was established through an Act of Congress signed by Abraham Lincoln in 1863. Zhang is the Patricia and James Poitras ’63 Professor in Neuroscience at MIT, an associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard. Scientists are elected to the National Academy of Sciences by members of the organization as recognition of their outstanding contributions to research.

“Because it comes from the scientific community, election to the National Academy of Sciences is a very special honor,” says Zhang, “and I’m grateful to all of my colleagues for the recognition and support.”

Zhang has revolutionized research across the life sciences by developing and sharing a number of powerful molecular biology tools, most notably, genome engineering tools based on the microbial CRISPR-Cas9 system. The simplicity and precision of Cas9 has led to its widespread adoption by researchers around the world. Indeed, the Zhang lab has shared more than 49,000 plasmids and reagents with more than 2,300 institutions across 62 countries through the non-profit plasmid repository Addgene.

Zhang continues to pioneer CRISPR-based technologies. For example, Zhang and his colleagues discovered new CRISPR systems that use a single enzyme to target RNA, rather than DNA. They have engineered these systems to achieve precise editing of single bases of RNA, enabling a wide range of applications in research, therapeutics, and biotechnology. Recently, he and his team also reported a highly sensitive nucleic acid detection system based on the CRISPR enzyme Cas13 that can be used in the field for monitoring pathogens and other molecular diagnostic applications.

Zhang has long shown a keen eye for recognizing the potential of transformative technologies and developing robust tools with broad utility. As a graduate student in Karl Diesseroth’s group at Stanford, he contributed to the development of optogenetics, a light-based technology that allows scientists to both track neurons and causally test outcomes of neuronal activity. Zhang also created an efficient system for reprogramming TAL effector proteins (TALEs) to specifically recognize and modulate target genes.

“Feng Zhang is unusually young to be elected into the National Academy of Science, which attests to the tremendous impact he is having on the field even at an early stage of his career, “ says Robert Desimone, director of the McGovern Institute for Brain Research at MIT.

This year the NAS, an organization that includes over 500 Nobel Laureates, elected 84 new members from across disciplines. The mission of the organization is to provide sound, objective advice on science to the nation, and to further the cause of science and technology in America. Four MIT professors were elected this year, with Amy Finkelstein (recognized for contributions to economics) as well as Mehran Karder and Xiao-Gang Wen (for their research in the realm of physics) also becoming members of the Academy.

The formal induction ceremony for new NAS members will be held at the Academy’s annual meeting in Washington D.C. next spring.

National Academy of Sciences elects four MIT professors for 2018

Anne Trafton |

Four MIT faculty members have been elected to the National Academy of Sciences (NAS) in recognition of their “distinguished and continuing achievements in original research.”

MIT’s four new NAS members are: Amy Finkelstein, the John and Jennie S. MacDonald Professor of Economics; Mehran Kardar, the Francis Friedman Professor of Physics; Xiao-Gang Wen, the Cecil and Ida Green Professor of Physics; and Feng Zhang, the Patricia and James Poitras ’63 Professor in Neuroscience at MIT, associate professor of brain and cognitive sciences and of biological engineering, and member of the McGovern Institute for Brain Research and the Broad Institute

The group was among 84 new members and 21 new foreign associates elected to the NAS. Membership in the NAS is one of the most significant honors given to academic researchers.

Amy Finkelstein

Finkelstein is the co-scientific director of J-PAL North America, the co-director of the Public Economics Program at the National Bureau of Economic Research, a member of the Institute of Medicine and the American Academy of Arts and Sciences, and a fellow of the Econometric Society.

She has received numerous awards and fellowships including the John Bates Clark Medal (2012), the American Society of Health Economists’ ASHEcon Medal (2014), a Presidential Early Career Award for Scientists and Engineers (2009), the American Economic Association’s Elaine Bennett Research Prize (2008) and a Sloan Research Fellowship (2007). She has also received awards for graduate student teaching (2012) and graduate student advising (2010) at MIT.

She is one of the two principal investigators for the Oregon Health Insurance Experiment, a randomized evaluation of the impact of extending Medicaid coverage to low income, uninsured adults.

Mehran Kardar

Kardar obtained a BA from Cambridge University in 1979 and a PhD in physics from MIT in 1983. He was a junior fellow of the Harvard Society of Fellows from 1983 to 1986 before returning to MIT as an assistant professor, and was promoted to full professor in 1996. He has been a visiting professor at a number of institutions including Catholic University in Belgium, Oxford University, the University of California at Santa Barbara, the University of California at Berkeley, and Ecole Normale Superieure in Paris.

His expertise is in statistical physics, and he has lectured extensively on this topic at MIT and in workshops at universities and institutes in France, the U.K., Switzerland, and Finland. He is the author of two books based on these lectures. In 2018 he was recognized by the American Association of Physics Teachers with the John David Jackson Excellence in Graduate Physics Education Award.

Kardar is a member of the founding board of the New England Complex Science Institute and the editorial board of Journal of Statistical Physics, and has helped organize Gordon Conference and KITP workshops. His awards include the Bergmann memorial research award, the A. P. Sloan Fellowship, the Presidential Young Investigator award, the Edgerton award for junior faculty achievements (MIT), and the Guggenheim Fellowship. He is a fellow of the American Physical Society and the American Academy of Arts and Sciences.

Xiao-Gang Wen

Wen received a BS in physics from University of Science and Technology of China in 1982 and a PhD in physics from Princeton University in 1987.

He studied superstring theory under theoretical physicist Edward Witten at Princeton University and later switched his research field to condensed matter physics while working with theoretical physicists Robert Schrieffer, Frank Wilczek, and Anthony Zee in the Institute for Theoretical Physics at the University of California at Santa Barbara (1987–1989). He became a five-year member of the Institute for Advanced Study at Princeton University in 1989 and joined MIT in 1991. Wen is the Cecil and Ida Green professor of Physics at MIT, a Distinguished Moore Scholar at Caltech, and a Distinguished Research Chair at the Perimeter Institute. In 2017 he received the Oliver E. Buckley Condensed Matter Physics Prize of the American Physical Society.

Wen’s main research area is condensed matter theory. His interests include strongly correlated electronic systems, topological order and quantum order, high-temperature superconductors, the origin and unification of elementary particles, and the Quantum Hall Effect and non-Abelian statistics.

Feng Zhang

Zhang is a bioengineer focused on developing tools to better understand nervous system function and disease. His lab applies these novel tools to interrogate gene function and study neuropsychiatric disorders in animal and stem cell models. Since joining MIT and the Broad Institute in January 2011, Zhang has pioneered the development of genome editing tools for use in eukaryotic cells — including human cells — from natural microbial CRISPR systems. He also developed a breakthrough technology called optogenetics with Karl Deisseroth at Stanford University and Edward Boyden, now of MIT.

Zhang joined MIT and the Broad Institute in 2011 and was awarded tenure in 2016. He received his BA in chemistry and physics from Harvard College and his PhD in chemistry from Stanford University. Zhang’s award include the Perl/UNC Prize in Neuroscience (2012, shared with Karl Deisseroth and Ed Boyden), the National Institutes of Health Director’s Pioneer Award (2012), the National Science Foundation’s Alan T. Waterman Award (2014), the Jacob Heskel Gabbay Award in Biotechnology and Medicine (2014, shared with Jennifer Doudna and Emmanuelle Charpentier), the Society for Neuroscience Young Investigator Award (2014), the Okazaki award, the Canada Gairdner International Award (shared with Doudna and Charpentier along with Philippe Horvath and Rodolphe Barrangou) and the 2016 Tang Prize (shared with Doudna and Charpentier).

Zhang is a founder of Editas Medicine, a genome editing company founded by world leaders in the fields of genome editing, protein engineering, and molecular and structural biology.

Eight from MIT elected to American Academy of Arts and Sciences for 2018

Anne Trafton |

Eight MIT faculty members are among 213 leaders from academia, business, public affairs, the humanities, and the arts elected to the American Academy of Arts and Sciences, the academy announced today.

One of the nation’s most prestigious honorary societies, the academy is also a leading center for independent policy research. Members contribute to academy publications, as well as studies of science and technology policy, energy and global security, social policy and American institutions, the humanities and culture, and education.

Those elected from MIT this year are:

  • Alexei Borodin, professor of mathematics;
  • Gang Chen, the Carl Richard Soderberg Professor of Power Engineering and head of the Department of Mechanical Engineering;
  • Larry D. Guth; professor of mathematics;
  • Parag A. Pathak, the Jane Berkowitz Carlton and Dennis William Carlton Professor of Microeconomics;
  • Nancy L. Rose, the Charles P. Kindleberger Professor of Applied Economics and head of the Department of Economics;
  • Leigh H. Royden, professor of earth, atmostpheric, and planetary sciences;
  • Sara Seager, the Class of 1941 Professor in the Department of Earth, Atmospheric and Planetary Sciences with a joint appointment in the Department of Physics; and
  • Feng Zhang, the James and Patricia Poitras Professor of Neuroscience within the departments of Brain and Cognitive Sciences and Biological Engineering, and an investigator at the McGovern Institute for Brain Research at MIT.

“This class of 2018 is a testament to the academy’s ability to both uphold our 238-year commitment to honor exceptional individuals and to recognize new expertise,” said Nancy C. Andrews, chair of the board of the American Academy.

“Membership in the academy is not only an honor, but also an opportunity and a responsibility,” added Jonathan Fanton, president of the American Academy. “Members can be inspired and engaged by connecting with one another and through academy projects dedicated to the common good. The intellect, creativity, and commitment of the 2018 class will enrich the work of the academy and the world in which we live.”

The new class will be inducted at a ceremony in October in Cambridge, Massachusetts.

Since its founding in 1780, the academy has elected leading “thinkers and doers” from each generation, including George Washington and Benjamin Franklin in the 18th century, Maria Mitchell and Daniel Webster in the 19th century, and Toni Morrison and Albert Einstein in the 20th century. The current membership includes more than 200 Nobel laureates and 100 Pulitzer Prize winners.

Researchers advance CRISPR-based tool for diagnosing disease

Anne Trafton |

The team that first unveiled the rapid, inexpensive, highly sensitive CRISPR-based diagnostic tool called SHERLOCK has greatly enhanced the tool’s power, and has developed a miniature paper test that allows results to be seen with the naked eye — without the need for expensive equipment.

 

The SHERLOCK team developed a simple paper strip to display test results for a single genetic signature, borrowing from the visual cues common in pregnancy tests. After dipping the paper strip into a processed sample, a line appears, indicating whether the target molecule was detected or not.

This new feature helps pave the way for field use, such as during an outbreak. The team has also increased the sensitivity of SHERLOCK and added the capacity to accurately quantify the amount of target in a sample and test for multiple targets at once. All together, these advancements accelerate SHERLOCK’s ability to quickly and precisely detect genetic signatures — including pathogens and tumor DNA — in samples.

Described today in Science, the innovations build on the team’s earlier version of SHERLOCK (shorthand for Specific High Sensitivity Reporter unLOCKing) and add to a growing field of research that harnesses CRISPR systems for uses beyond gene editing. The work, led by researchers from the Broad Institute of MIT and Harvard and from MIT, has the potential for a transformative effect on research and global public health.

“SHERLOCK provides an inexpensive, easy-to-use, and sensitive diagnostic method for detecting nucleic acid material — and that can mean a virus, tumor DNA, and many other targets,” said senior author Feng Zhang, a core institute member of the Broad Institute, an investigator at the McGovern Institute, and the James and Patricia Poitras ’63 Professor in Neuroscience and associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT. “The SHERLOCK improvements now give us even more diagnostic information and put us closer to a tool that can be deployed in real-world applications.”

The researchers previously showcased SHERLOCK’s utility for a range of applications. In the new study, the team uses SHERLOCK to detect cell-free tumor DNA in blood samples from lung cancer patients and to detect synthetic Zika and Dengue virus simultaneously, in addition to other demonstrations.

Clear results on a paper strip

“The new paper readout for SHERLOCK lets you see whether your target was present in the sample, without instrumentation,” said co-first author Jonathan Gootenberg, a Harvard graduate student in Zhang’s lab as well as the lab of Broad core institute member Aviv Regev. “This moves us much closer to a field-ready diagnostic.”

The team envisions a wide range of uses for SHERLOCK, thanks to its versatility in nucleic acid target detection. “The technology demonstrates potential for many health care applications, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer, but it can also be used for industrial and agricultural applications where monitoring steps along the supply chain can reduce waste and improve safety,” added Zhang.

At the core of SHERLOCK’s success is a CRISPR-associated protein called Cas13, which can be programmed to bind to a specific piece of RNA. Cas13’s target can be any genetic sequence, including viral genomes, genes that confer antibiotic resistance in bacteria, or mutations that cause cancer. In certain circumstances, once Cas13 locates and cuts its specified target, the enzyme goes into overdrive, indiscriminately cutting other RNA nearby. To create SHERLOCK, the team harnessed this “off-target” activity and turned it to their advantage, engineering the system to be compatible with both DNA and RNA.

SHERLOCK’s diagnostic potential relies on additional strands of synthetic RNA that are used to create a signal after being cleaved. Cas13 will chop up this RNA after it hits its original target, releasing the signaling molecule, which results in a readout that indicates the presence or absence of the target.

Multiple targets and increased sensitivity

The SHERLOCK platform can now be adapted to test for multiple targets. SHERLOCK initially could only detect one nucleic acid sequence at a time, but now one analysis can give fluorescent signals for up to four different targets at once — meaning less sample is required to run through diagnostic panels. For example, the new version of SHERLOCK can determine in a single reaction whether a sample contains Zika or dengue virus particles, which both cause similar symptoms in patients. The platform uses Cas13 and Cas12a (previously known as Cpf1) enzymes from different species of bacteria to generate the additional signals.

SHERLOCK’s second iteration also uses an additional CRISPR-associated enzyme to amplify its detection signal, making the tool more sensitive than its predecessor. “With the original SHERLOCK, we were detecting a single molecule in a microliter, but now we can achieve 100-fold greater sensitivity,” explained co-first author Omar Abudayyeh, an MIT graduate student in Zhang’s lab at Broad. “That’s especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low. This next generation of features help make SHERLOCK a more precise system.”

The authors have made their reagents available to the academic community through Addgene and their software tools can be accessed via the Zhang lab website and GitHub.

This study was supported in part by the National Institutes of Health and the Defense Threat Reduction Agency.

Polina Anikeeva and Feng Zhang awarded 2018 Vilcek Prize

Anne Trafton |

Polina Anikeeva, the Class of 1942 Associate Professor in the Department of Materials Science and Engineering and associate director of the Research Laboratory of Electronics, and Feng Zhang, the James and Patricia Poitras ’63 Professor in Neuroscience at the McGovern Institute, have each been awarded a 2018 Vilcek Prize for Creative Promise in Biomedical Science. Awarded annually by the Vilcek Foundation, the $50,000 prizes recognize younger immigrants who have demonstrated exceptional promise early in their careers.

“The Vilcek Prizes were established in appreciation of the immigrants who chose to dedicate their vision and talent to bettering American society,” says Rick Kinsel, president of the Vilcek Foundation. “This year’s prizewinners honor and continue that legacy with works of astounding, revolutionary importance.”

Polina Anikeeva, who was born in the former Soviet Union, earned her PhD in materials science and engineering at MIT in 2009 and now runs her own bioelectronics lab in the same department focused on the development of materials and devices that enable recording and manipulation of signaling processes within the nervous system. The Vilcek Foundation recognizes Anikeeva for “fashioning ingenious solutions to long-standing challenges in biomedical engineering” including the design of therapeutic devices for conditions such as Parkinson’s disease and spinal cord injury.

Feng Zhang, who is also a core member of the Broad Institute and an associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, is being recognized for his role in advancing optogenetics (a method for controlling brain activity with light) and developing molecular tools to edit the genome. Thanks to his leadership in inventing precise and efficient gene-editing technologies using CRISPR, Zhang’s work has resulted in a “growing array of applications, such as uncovering the genetic underpinnings of diseases, ushering in gene therapies to cure heritable diseases, and improving agriculture.” Zhang’s family immigrated to the United States from China when he was 11 years of age.

Anikeeva and Zhang will be among eight Vilcek prizewinners honored at an awards gala in New York City in April 2018.

The Vilcek Foundation was established in 2000 by Jan and Marica Vilcek, immigrants from the former Czechoslovakia. The mission of the foundation, to honor the contributions of immigrants to the United States and to foster appreciation of the arts and sciences, was inspired by the couple’s respective careers in biomedical science and art history, as well as their personal experiences and appreciation of the opportunities they received as newcomers to this country.

Researchers engineer CRISPR to edit single RNA letters in human cells

Anne Trafton |

The Broad Institute and MIT scientists who first harnessed CRISPR for mammalian genome editing have engineered a new molecular system for efficiently editing RNA in human cells. RNA editing, which can alter gene products without making changes to the genome, has profound potential as a tool for both research and disease treatment.

In a paper published today in Science, senior author Feng Zhang and his team describe the new CRISPR-based system, called RNA Editing for Programmable A to I Replacement, or “REPAIR.” The system can change single RNA nucleotides in mammalian cells in a programmable and precise fashion. REPAIR has the ability to reverse disease-causing mutations at the RNA level, as well as other potential therapeutic and basic science applications.

“The ability to correct disease-causing mutations is one of the primary goals of genome editing,” says Zhang, a core institute member of the Broad Institute, an investigator at the McGovern Institute, and the James and Patricia Poitras ’63 Professor in Neuroscience and associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT. “So far, we’ve gotten very good at inactivating genes, but actually recovering lost protein function is much more challenging. This new ability to edit RNA opens up more potential opportunities to recover that function and treat many diseases, in almost any kind of cell.”

REPAIR has the ability to target individual RNA letters, or nucleosides, switching adenosines to inosines (read as guanosines by the cell). These letters are involved in single-base changes known to regularly cause disease in humans. In human disease, a mutation from G to A is extremely common; these alterations have been implicated in, for example, cases of focal epilepsy, Duchenne muscular dystrophy, and Parkinson’s disease. REPAIR has the ability to reverse the impact of any pathogenic G-to-A mutation regardless of its surrounding nucleotide sequence, with the potential to operate in any cell type.

Unlike the permanent changes to the genome required for DNA editing, RNA editing offers a safer, more flexible way to make corrections in the cell. “REPAIR can fix mutations without tampering with the genome, and because RNA naturally degrades, it’s a potentially reversible fix,” explains co-first author David Cox, a graduate student in Zhang’s lab.

To create REPAIR, the researchers systematically profiled the CRISPR-Cas13 enzyme family for potential “editor” candidates (unlike Cas9, the Cas13 proteins target and cut RNA). They selected an enzyme from Prevotella bacteria, called PspCas13b, which was the most effective at inactivating RNA. The team engineered a deactivated variant of PspCas13b that still binds to specific stretches of RNA but lacks its “scissor-like” activity, and fused it to a protein called ADAR2, which changes the letters A to I in RNA transcripts.

In REPAIR, the deactivated Cas13b enzyme seeks out a target sequence of RNA, and the ADAR2 element performs the base conversion without cutting the transcript or relying on any of the cell’s native machinery.

The team further modified the editing system to improve its specificity, reducing detectable off-target edits from 18,385 to only 20 in the whole transcriptome. The upgraded incarnation, REPAIRv2, consistently achieved the desired edit in 20 to 40 percent — and up to 51 percent — of a targeted RNA without signs of significant off-target activity. “The success we had engineering this system is encouraging, and there are clear signs REPAIRv2 can be evolved even further for more robust activity while still maintaining specificity,” says Omar Abudayyeh, co-first author and a graduate student in Zhang’s lab. Cox and Abudayyeh are both students in the Harvard-MIT Program in Health Sciences and Technology.

To demonstrate REPAIR’s therapeutic potential, the team synthesized the pathogenic mutations that cause Fanconi anemia and X-linked nephrogenic diabetes insipidus, introduced them into human cells, and successfully corrected these mutations at the RNA level. To push the therapeutic prospects further, the team plans to improve REPAIRv2’s efficiency and to package it into a delivery system appropriate for introducing REPAIRv2 into specific tissues in animal models.

The researchers are also working on additional tools for other types of nucleotide conversions. “There’s immense natural diversity in these enzymes,” says co-first author Jonathan Gootenberg, a graduate student in both Zhang’s lab and the lab of Broad core institute member Aviv Regev. “We’re always looking to harness the power of nature to carry out these changes.”

Zhang, along with the Broad Institute and MIT, plans to share the REPAIR system widely. As with earlier CRISPR tools, the groups will make this technology freely available for academic research via the Zhang lab’s page on the plasmid-sharing website Addgene, through which the Zhang lab has already shared reagents more than 42,000 times with researchers at more than 2,200 labs in 61 countries, accelerating research around the world.

This research was funded, in part, by the National Institutes of Health and the Poitras Center for Affective Disorders Research.

Ten researchers from MIT and Broad receive NIH Director’s Awards

Anne Trafton |

The High-Risk, High-Reward Research (HRHR) program, supported by the National Institutes of Health (NIH) Common Fund, has awarded 86 grants to scientists with unconventional approaches to major challenges in biomedical and behavioral research. Ten of the awardees are affiliated with MIT and the Broad Institute of MIT and Harvard.

The NIH typically supports research projects, not individual scientists, but the HRHR program identifies specific researchers with innovative ideas to address gaps in biomedical research. The program issues four types of awards annually — the Pioneer Award, the New Innovator Award, the Transformative Research Award and the Early Independence Award — to “high-caliber investigators whose ideas stretch the boundaries of our scientific knowledge.”

Four researchers who are affiliated with either MIT or the Broad Institute received this year’s New Innovator Awards, which support “unusually innovative research” from early career investigators. They are:

  • Paul Blainey, an MIT assistant professor of biological engineering and a core member of the Broad Institute, is an expert in microanalysis systems for studies of individual molecules and cells. The award will fund the establishment a new technology that enables advanced readout from living cells.
  • Kevin Esvelt, an associate professor of media arts and sciences at MIT’s Media Lab, invents new ways to study and influence the evolution of ecosystems. Esvelt plans to use the NIH grant to develop powerful “daisy drive” systems for more precise genetic alterations of wild organisms. Such an intervention has the potential to serve as a powerful weapon against malaria, Zika, Lyme disease, and many other infectious diseases.
  • Evan Macosko is an associate member of the Broad Institute who develops molecular techniques to more deeply understand the function of cellular specialization in the nervous system. Macosko’s award will fund a novel technology, Slide-seq, which enables genome-wide expression analysis of brain tissue sections at single-cell resolution.
  • Gabriela Schlau-Cohen, an MIT assistant professor of chemistry, combines tools from chemistry, optics, biology, and microscopy to develop new approaches to study the dynamics of biological systems. Her award will be used to fund the development of a new nanometer-distance assay that directly accesses protein motion with unprecedented spatiotemporal resolution under physiological conditions.

Recipients of the Early Independence Award include three Broad Institute Fellows. The award recognizes “exceptional junior scientists” with an opportunity to skip traditional postdoctoral training and move immediately into independent research positions.

  • Ahmed Badran is a Broad Institute Fellow who studies the function of ribosomes and the control of protein synthesis. Ribosomes are important targets for antibiotics, and the NIH award will support the development of a new technology platform for probing ribosome function within living cells.
  • Fei Chen, a Broad Institute Fellow who is also a research affiliate at MIT’s McGovern Institute for Brain Research, has pioneered novel molecular and microscopy tools to illuminate biological pathways and function. He will use one of these tools, expansion microscopy, to explore the molecular basis of glioblastomas, an aggressive form of brain cancer.
  • Hilary Finucane, a Broad Institute Fellow who recently received her PhD from MIT’s Department of Mathematics, develops computational methods for analyzing biological data. She plans to develop methods to analyze large-scale genomic data to identify disease-relevant cell types and tissues, a necessary first step for understanding molecular mechanisms of disease.

Among the recipients of the NIH’s Pioneer Awards are Kay Tye, an assistant professor of brain and cognitive sciences at MIT and a member of MIT’s Picower Institute for Learning and Memory, and Feng Zhang, the James and Patricia Poitras ’63 Professor in Neuroscience, an associate professor of brain and cognitive sciences and biological engineering at MIT, a core member of the Broad Institute, and an investigator at MIT’s McGovern Institute for Brain Research. Recipients of this award are challenged to pursue “groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. Tye, who studies the brain mechanisms underlying emotion and behavior, will use her award to look at the neural representation of social homeostasis and social rank. Zhang, who pioneered the gene-editing technology known as CRISPR, plans to develop a suite of tools designed to achieve precise genome surgery for repairing disease-causing changes in DNA.

Ed Boyden, an associate professor of brain and cognitive sciences and biological engineering at MIT, and a member of MIT’s Media Lab and McGovern Institute for Brain Research, is a recipient of the Transformative Research Award. This award promotes “cross-cutting, interdisciplinary approaches that could potentially create or challenge existing paradigms.” Boyden, who develops new strategies for understanding and engineering brain circuits, will use the grant to develop high-speed 3-D imaging of neural activity.

This year, the NIH issued a total of 12 Pioneer Awards, 55 New Innovator Awards, 8 Transformative Research Awards, and 11 Early Independence Awards. The awards total $263 million and represent contributions from the NIH Common Fund; National Institute of General Medical Sciences; National Institute of Mental Health; National Center for Complementary and Integrative Health; and National Institute of Dental and Craniofacial Research.

“I continually point to this program as an example of the creative and revolutionary research NIH supports,” said NIH Director Francis S. Collins. “The quality of the investigators and the impact their research has on the biomedical field is extraordinary.”

Gene-editing technology developer Feng Zhang awarded $500,000 Lemelson-MIT Prize

Anne Trafton |

Feng Zhang, a pioneer of the revolutionary CRISPR gene-editing technology, TAL effector proteins, and optogenetics, is the recipient of the 2017 $500,000 Lemelson-MIT Prize, the largest cash prize for invention in the United States. Zhang is a core member of the Broad Institute of MIT and Harvard, an investigator at the McGovern Institute for Brain Research, the James and Patricia Poitras Professor in Neuroscience at MIT, and associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT.

Zhang and his team were first to develop and demonstrate successful methods for using an engineered CRISPR-Cas9 system to edit genomes in living mouse and human cells and have turned CRISPR technology into a practical and shareable collection of tools for robust gene editing and epigenomic manipulation. CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, has been harnessed by Zhang and his team as a groundbreaking gene-editing tool that is simple and versatile to use. A key tenet of Zhang’s is to encourage further development and research through open sharing of tools and scientific collaboration. Zhang believes that wide use of CRISPR-based tools will further our understanding of biology, allowing scientists to identify genetic differences that contribute to diseases and, eventually, provide the basis for new therapeutic techniques.

Zhang’s lab has trained thousands of researchers to use CRISPR technology, and since 2013 he has shared over 40,000 plasmid samples with labs around the world both directly and through the nonprofit Addgene, enabling wide use of his CRISPR tools in their research.

Zhang began working in a gene therapy laboratory at the age of 16 and has played key roles in the development of multiple technologies. Prior to harnessing CRISPR-Cas9, Zhang engineered microbial TAL effectors (TALEs) for use in mammalian cells, working with colleagues at Harvard University, authoring multiple publications on the subject and becoming a co-inventor on several patents on TALE-based technologies. Zhang was also a key member of the team at Stanford University that harnessed microbial opsins for developing optogenetics, which uses light signals and light-sensitive proteins to monitor and control activity in brain cells. This technology can help scientists understand how cells in the brain affect mental and neurological illnesses. Zhang has co-authored multiple publications on optogenetics and is a co-inventor on several patents related to this technology.

Zhang’s numerous scientific discoveries and inventions, as well as his commitment to mentorship and collaboration, earned him the Lemelson-MIT Prize, which honors outstanding mid-career inventors who improve the world through technological invention and demonstrate a commitment to mentorship in science, technology, engineering and mathematics (STEM).

“Feng’s creativity and dedication to problem-solving impressed us,” says Stephanie Couch, executive director of the Lemelson-MIT Program. “Beyond the breadth of his own accomplishments, Feng and his lab have also helped thousands of scientists across the world access the new technology to advance their own scientific discoveries.”

“It is a tremendous honor to receive the Lemelson-MIT Prize and to join the company of so many incredibly impactful inventors who have won this prize in years past,” says Zhang. “Invention has always been a part of my life; I think about new problems every day and work to solve them creatively. This prize is a testament to the passionate work of my team and the support of my family, teachers, colleagues and counterparts around the world.”

The $500,000 prize, which bears no restrictions in how it can be used, is made possible through the support of The Lemelson Foundation, the world’s leading funder of invention in service of social and economic change.

“We are thrilled to honor Dr. Zhang, who we commend for his advancements in genetics, and more importantly, his willingness to share his discoveries to advance the work of others around the world,” says Dorothy Lemelson, chair of The Lemelson Foundation. “Zhang’s work is inspiring a new generation of inventors to tackle the biggest problems of our time.”

Zhang will speak at EmTech MIT, the annual conference on emerging technologies hosted by MIT Technology Review at the MIT Media Lab on Tuesday, Nov. 7.

The Lemelson-MIT Program is now seeking nominations for the 2018 $500,000 Lemelson-MIT Prize. Please contact the Lemelson-MIT Program at awards-lemelson@mit.edu for more information or visit the MIT-Lemelson Prize website.

Feng Zhang Wins the 2017 Blavatnik National Award for Young Scientists

Anne Trafton |

The Blavatnik Family Foundation and the New York Academy of Sciences today announced the 2017 Laureates of the Blavatnik National Awards for Young Scientists. Starting with a pool of 308 nominees – the most promising scientific researchers aged 42 years and younger nominated by America’s top academic and research institutions – a distinguished jury first narrowed their selections to 30 Finalists, and then to three outstanding Laureates, one each from the disciplines of Life Sciences, Chemistry and Physical Sciences & Engineering. Each Laureate will receive $250,000 – the largest unrestricted award of its kind for early career scientists and engineers. This year’s Blavatnik National Laureates are:

Feng Zhang, PhD, Core Member, Broad Institute of MIT and Harvard; Associate Professor of Brain and Cognitive Sciences and Biomedical Engineering, MIT; Robertson Investigator, New York Stem Cell Foundation; James and Patricia Poitras ’63 Professor in Neuroscience, McGovern Institute for Brain Research at MIT. Dr. Zhang is being recognized for his role in developing the CRISPR-Cas9 gene-editing system and demonstrating pioneering uses in mammalian cells, and for his development of revolutionary technologies in neuroscience.

Melanie S. Sanford, PhD, Moses Gomberg Distinguished University Professor and Arthur F. Thurnau Professor of Chemistry, University of Michigan. Dr. Sanford is being celebrated for developing simpler chemical approaches – with less environmental impact – to the synthesis of molecules that have applications ranging from carbon dioxide recycling to drug discovery.

Yi Cui, PhD, Professor of Materials Science and Engineering, Photon Science and Chemistry, Stanford University and SLAC National Accelerator Laboratory. Dr. Cui is being honored for his technological innovations in the use of nanomaterials for environmental protection and the development of sustainable energy sources.

“The work of these three brilliant Laureates demonstrates the exceptional science being performed at America’s premiere research institutions and the discoveries that will make the lives of future generations immeasurably better,” said Len Blavatnik, Founder and Chairman of Access Industries, head of the Blavatnik Family Foundation, and an Academy Board Governor.

“Each of our 2017 National Laureates is shifting paradigms in areas that profoundly affect the way we tackle the health of our population and our planet — improved ways to store energy, “greener” drug and fuel production, and novel tools to correct disease-causing genetic mutations,” said Ellis Rubinstein, President and CEO of the Academy and Chair of the Awards’ Scientific Advisory Council. “Recognition programs like the Blavatnik Awards provide incentives and resources for rising stars, and help them to continue their important work. We look forward to learning where their innovations and future discoveries will take us in the years ahead.”

The annual Blavatnik Awards, established in 2007 by the Blavatnik Family Foundation and administered by the New York Academy of Sciences, recognize exceptional young researchers who will drive the next generation of innovation by answering today’s most complex and intriguing scientific questions.

Scientists unveil CRISPR-based diagnostic platform

Anne Trafton |

A team of scientists from the Broad Institute of MIT and Harvard, the McGovern Institute for Brain Research at MIT, the Institute for Medical Engineering and Science at MIT, and the Wyss Institute for Biologically Inspired Engineering at Harvard University has adapted a CRISPR protein that targets RNA (rather than DNA), for use as a rapid, inexpensive, highly sensitive diagnostic tool with the potential to transform research and global public health.

In a study published today in Science, Broad Institute members Feng Zhang, Jim Collins, Deb Hung, Aviv Regev, and Pardis Sabeti describe how this RNA-targeting CRISPR enzyme was harnessed as a highly sensitive detector — able to indicate the presence of as little as a single molecule of a target RNA or DNA. Co-first authors Omar Abudayyeh and Jonathan Gootenberg, graduate students at MIT and Harvard, respectively, dubbed the new tool SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing); this technology could one day be used to respond to viral and bacterial outbreaks, monitor antibiotic resistance, and detect cancer.

The scientists demonstrate the method’s versatility on a range of applications, including:

• detecting the presence of Zika virus in patient blood or urine samples within hours;
• distinguishing between the genetic sequences of African and American strains of Zika virus;
• discriminating specific types of bacteria, such as E. coli;
• detecting antibiotic resistance genes;
• identifying cancerous mutations in simulated cell-free DNA fragments; and
• rapidly reading human genetic information, such as risk of heart disease, from a saliva sample.

Because the tool can be designed for use as a paper-based test that does not require refrigeration, the researchers say it is well-suited for fast deployment and widespread use inside and outside of traditional settings — such as at a field hospital during an outbreak, or a rural clinic with limited access to advanced equipment.

“It’s exciting that the Cas13a enzyme, which was originally identified in our collaboration with Eugene Koonin to study the basic biology of bacterial immunity, can be harnessed to achieve such extraordinary sensitivity, which will be powerful for both science and clinical medicine,” says Feng Zhang, core institute member of the Broad Institute, an investigator at the McGovern Institute, and the James and Patricia Poitras ’63 Professor in Neuroscience and associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT.

In June 2016, Zhang and his colleagues first characterized the RNA-targeting CRISPR enzyme, now called Cas13a (previously known as C2c2), which can be programmed to cleave particular RNA sequences in bacterial cells. Unlike DNA-targeting CRISPR enzymes (such as Cas9 and Cpf1), Cas13a can remain active after cutting its intended RNA target and may continue to cut other nontargeted RNAs in a burst of activity that Zhang lab scientists referred to as “collateral cleavage.” In their paper and patent filing, the team described a wide range of biotechnological applications for the system, including harnessing RNA cleavage and collateral activity for basic research, diagnostics, and therapeutics.

In a paper in Nature in September 2016, Jennifer Doudna, Alexandra East-Seletsky, and their colleagues at the University of California at Berkeley employed the Cas13a collateral cleavage activity for RNA detection. That method required the presence of many millions of molecules, however, and therefore lacked the sensitivity required for many research and clinical applications.

The method reported today is a million-fold more sensitive. This increase was the result of a collaboration between Zhang and his team and Broad Institute member Jim Collins, who had been working on diagnostics for Zika virus.

Working together, the Zhang and Collins teams were able to use a different amplification process, relying on body heat, to boost the levels of DNA or RNA in their test samples. Once the level was increased, the team applied a second amplification step to convert the DNA to RNA, which enabled them to increase the sensitivity of the RNA-targeting CRISPR by a millionfold, all with a tool that can be used in nearly any setting.

“We can now effectively and readily make sensors for any nucleic acid, which is incredibly powerful when you think of diagnostics and research applications,” says Collins, the Termeer Professor of Medical Engineering and Science at MIT and core faculty member at the Wyss Institute. “This tool offers the sensitivity that could detect an extremely small amount of cancer DNA in a patient’s blood sample, for example, which would help researchers understand how cancer mutates over time. For public health, it could help researchers monitor the frequency of antibiotic-resistant bacteria in a population. The scientific possibilities get very exciting very quickly.”

One of the most urgent and obvious applications for this new diagnostic tool would be as a rapid, point-of-care diagnostic for infectious disease outbreaks in resource-poor areas.
“There is great excitement around this system,” says Deb Hung, co-author and co-director of the Broad’s Infectious Disease and Microbiome Program. “There is still much work to be done, but if SHERLOCK can be developed to its full potential it could fundamentally change the diagnosis of common and emerging infectious diseases.”

“One thing that’s especially powerful about SHERLOCK is its ability to start testing without a lot of complicated and time-consuming upstream experimental work,” says Pardis Sabeti, also a co-author in the paper. In the wake of the ongoing Zika outbreak, Sabeti and the members of her lab have been working to collect samples, rapidly sequence genomes, and share data in order to accelerate the outbreak response effort. “This ability to take raw samples and immediately start processing could transform the diagnosis of Zika and a boundless number of other infectious diseases,” she says. “This is just the beginning.”

Additional authors include Jeong Wook Lee, Patrick Essletzbichler, Aaron J. Dy, Julia Joung, Vanessa Verdine, Nina Donghia, Nichole M. Daringer, Catherine A. Freije, Cameron Myhrvold, Roby P. Bhattacharyya, Jonathan Livny, and Eugene V. Koonin.