This animation depicts how Cas13 — a CRISPR-associated protein — may be adapted to detect human disease. This new diagnostic tool, called SHERLOCK, targets RNA (rather than DNA), and has the potential to transform research and global public health.
Researcher: Feng Zhang
Feng Zhang wins 2018 Keio Medical Science Prize
Molecular biologist Feng Zhang has been named a winner of the prestigious Keio Medical Science Prize. He is being recognized for the groundbreaking development of CRISPR-Cas9-mediated genome engineering in cells and its application for medical science.
Zhang is the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, a Howard Hughes Medical Institute investigator, an investigator at the McGovern Institute for Brain Research, and a core member of the Broad Institute of MIT and Harvard.
“We are delighted that Feng is now a Keio Prize laureate,” says McGovern Institute Director Robert Desimone. “This truly recognizes the remarkable achievements that he has made at such a young age.”
Zhang is a molecular biologist who has contributed to the development of multiple molecular tools to accelerate the understanding of human disease and create new therapeutic modalities. During his graduate work, Zhang contributed to the development of optogenetics, a system for activating neurons using light, which has advanced our understanding of brain connectivity.
Zhang went on to pioneer the deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use across the life sciences and it has groundbreaking implications for disease therapeutics, biotechnology, and agriculture. He has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA, and may potentially be a way to treat genetic diseases without altering the genome. Zhang has also developed a molecular detection system called SHERLOCK based on the Cas13 family, which can sense trace amounts of genetic material, including viruses and alterations in genes that might be linked to cancer.
“I am tremendously honored to have our work recognized by the Keio Medical Prize,” says Zhang. “It is an inspiration to us to continue our work to improve human health.”
Now in its 23rd year, the Keio Medical Science Prize is awarded to a maximum of two scientists each year. The other 2018 laureate, Masashi Yanagisawa, director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba, is being recognized for his seminal work on sleep control mechanisms.
The prize is offered by Keio University, and the selection committee specifically looks for laureates that have made an outstanding contribution to medicine or the life sciences. The prize was initially endowed by Mitsunada Sakaguchi in 1994, with the express condition that it be used to commend outstanding science, promote advances in medicine and the life sciences, expand researcher networks, and contribute to the wellbeing of humankind. The winners receive a certificate of merit, a medal, and a monetary award of approximately $90,000.
The prize ceremony will be held on Dec. 18 at Keio University in Tokyo.
Feng Zhang named winner of the 2018 Keio Medical Science Prize
Feng Zhang and Masashi Yanagisawa have been named the 2018 winners of the prestigious Keio Medical Science Prize. Zhang is being recognized for the groundbreaking development of CRISPR-Cas9-mediated genome engineering in cells and its application for medical science. Zhang is an HHMI Investigator and the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in MIT’s 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. Masashi Yanagisawa, Director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba, is being recognized for his seminal work on sleep control mechanisms.
“We are delighted that Feng is now a Keio Prize laureate,” says McGovern Institute Director Robert Desimone. “This truly recognizes the remarkable achievements that he has made at such a young age.”
The Keio Medical Prize is awarded to a maximum of two scientists each year, and is now in its 23rd year. The prize is offered by Keio University, and the selection committee specifically looks for laureates that have made an outstanding contribution to medicine or the life sciences. The prize was initially endowed by Dr. Mitsunada Sakaguchi in 1994, with the express condition that it be used to commend outstanding science, promote medical advances in medicine and the life sciences, expand researcher networks, and contribute to the well-being of humankind. The winners receive a certificate of merit, medal, and a monetary award of 10 million yen.
Feng Zhang is a molecular biologist who has contributed to the development of multiple molecular tools to accelerate our understanding of human disease and create new therapeutic modalities. During his graduate work Zhang contributed to the development of optogenetics, a system for activating neurons using light, which has advanced our understanding of brain connectivity. Zhang went on to pioneer the deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use across the life sciences and it has groundbreaking implications for disease therapeutics, biotechnology, and agriculture. Zhang has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA, and may potentially be a way to treat genetic diseases without altering the genome. He has also developed a molecular detection system called SHERLOCK based on the Cas13 family, which can sense trace amounts of genetic material, including viruses and alterations in genes that might be linked to cancer.
“I am tremendously honored to have our work recognized by the Keio Medical Prize,” says Zhang. “It is an inspiration to us to continue our work to improve human health.”
The prize ceremony will be held on December 18th 2018 at Keio University in Tokyo, Japan.
Advancing knowledge in medical and genetic sciences
Research proposals from Laurie Boyer, associate professor of biology; Matt Shoulders, the Whitehead Career Development Associate Professor of Chemistry; and Feng Zhang, associate professor in the departments of Brain and Cognitive Sciences and Biological Engineering, Patricia and James Poitras ’63 Professor in Neuroscience, investigator at the McGovern Institute for Brain Research, and core member of the Broad Institute, have recently been selected for funding by the G. Harold and Leila Y. Mathers Foundation. These three grants from the Mathers Foundation will enable, over the next three years, key projects in the researchers’ respective labs.
Regenerative medicine holds great promise for treating heart failure, but that promise is unrealized, in part, due to a lack of sufficient understanding of heart development at the mechanistic level. Boyer’s research aims to achieve a deep, mechanistic understanding of the gene control switches that coordinate normal heart development. She then aims to leverage this knowledge and design effective strategies for rewiring faulty circuits in aging and disease.
“We are very grateful to receive support and recognition of our work from the Mathers Foundation,” said Boyer. “This award will allow us to build upon our prior work and to embark upon high risk projects that could ultimately change how we think about treating diseases resulting from faulty wiring of gene expression programs.”
Shoulders’ goal, with this support from the Mathers Foundation, is to elucidate underlying causes of osteoarthritis. There is currently no cure for osteoarthritis, which is perhaps the most common aging-related disease and is characterized by a progressive deterioration of joint cartilage culminating in inflammation, debilitating pain, and joint dysfunction. The Shoulders Group aims to test a new model for osteoarthritis — specifically, the concept that a collapse of proteostasis in aging cartilage cells creates an unrecoverable cartilage repair defect, thus initiating a self-amplifying, destructive feedback loop leading to pathology. Proteostasis collapse in aging cells is a well-known, disease-causing phenomenon that has previously been considered primarily in the context of neurodegenerative disorders. If correct, the proteostasis collapse model for osteoarthritis could one day lead to a novel class of therapeutic options for the disease.
“We are delighted to receive this generous support from the Mathers Foundation, which makes it possible for us to pursue an outside-the-box, high-risk/high-impact idea regarding the origins of osteoarthritis,” said Shoulders. “The research we are now able to pursue will not only provide fundamental, molecular-level insights into joint function, but also could change how we think about this widespread disease.”
Many genetic diseases are caused by the change of just a single base of DNA. Zhang is a leader in the field of genome editing, and he and his team have developed an array of tools based on the microbial immune CRISPR-Cas systems that can manipulate DNA and RNA in human cells. Together, these tools are changing the way molecular biology research is conducted, and they hold immense potential as therapeutic agents to correct thousands of genetic diseases. Now, with the support of the Mathers Foundation, Zhang is working to realize this potential by developing a CRISPR-based therapeutic that works at the level of RNA and offers a safe, effective route to treating a range of diseases, including diseases of the brain and central nervous system, which are difficult to treat with existing gene therapies.
“The generous support from the Mathers Foundation allows us the freedom to explore this exciting new direction for CRISPR-based technologies,” Zhang stated.
Known for their generosity and philanthropy, G. Harold and Leila Y. Mathers created their foundation with the goal of distributing their wealth among sustainable, charitable causes, with a particular interest in basic scientific research. The Mathers Foundation, whose ongoing mission is to advance knowledge in the life sciences by sponsoring scientific research and applying learnings and discoveries to benefit mankind, has issued grants since 1982.
Ed Boyden and Feng Zhang named Howard Hughes Medical Institute Investigators
Two members of the MIT faculty were named Howard Hughes Medical Institute (HHMI) investigators today. Ed Boyden and Feng Zhang join a community of 300 HHMI scientists who are “transforming biology and medicine, one discovery at a time.” Both researchers have been instrumental in recognizing, developing, and sharing robust tools with broad utility that have revolutionized the life sciences.
“We are thrilled that Ed and Feng are being recognized in this way” says Robert Desimone, director of the McGovern Institute for Brain Research at MIT. “Being named to the investigator program recognizes their previous achievements and allows them to follow the innovative path that is a trait of their research.”
HHMI selects new Investigators to join its flagship program through periodic competitions. In choosing researchers to join its investigator program, HHMI specifically aims to select ‘people, not projects’ and identifies trail blazers in the biomedical sciences. The organization provides support for an unusual length of time, seven years with a renewal process at the end of that period, thus giving selected scientists the time and freedom to tackle difficult and important biological questions. HHMI-affiliated scientists continue to work at their home institution. The HHMI Investigator program currently funds 300 scientists at 60 research institutions across the United States.
Ed Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, has pioneered a number of technologies that allow visualization and manipulation of complex biological systems. Boyden worked, along with Karl Deisseroth and Feng Zhang, on optogenetics, a system that leverages microbial opsins to manipulate neuronal activity using light. This technology has transformed our ability to examine neuronal function in vivo. Boyden’s work initiated optogenetics, then extended it into a multicolor, high-speed, and noninvasive toolbox. Subsequent technological advances developed by Boyden and his team include expansion microscopy, an imaging strategy that overcomes the limits of light microscopy by expanding biological specimens in a controlled fashion. Boyden’s team also recently developed a directed evolution system that is capable of robotically screening hundreds of thousands of mutated proteins for specific properties within hours. He and his team recently used the system to develop a high-performance fluorescent voltage indicator.
“I am honored and excited to become an HHMI investigator,” says Boyden, who is also a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research and an associate professor in the Program in Media Arts and Sciences at the MIT Media Lab; the MIT Department of Brain and Cognitive Sciences; and the MIT Department of Biological Engineering. “This will give my group the ability to open up completely new areas of science, in a way that would not be possible with traditional funding.”
Feng Zhang is a molecular biologist focused on building new tools for probing the human brain. As a graduate student, Zhang was part of the team that developed optogenetics. Zhang went on to develop other innovative tools. These achievements include the landmark deployment of the microbial CRISPR-Cas9 system for genome engineering in eukaryotic cells. The ease and specificity of the system has led to its widespread use. Zhang has continued to mine bacterial CRISPR systems for additional enzymes with useful properties, leading to the discovery of Cas13, which targets RNA, rather than DNA. By leveraging the unique properties of Cas13, Zhang and his team created a precise RNA editing tool, which may potentially be a safer way to treat genetic diseases because the genome does not need to be cut, as well as a molecular detection system, termed SHERLOCK, which can sense trace amounts of genetic material, such as viruses.
“It is so exciting to join this exceptional scientific community,” says Zhang, “and be given this opportunity to pursue our research into engineering natural systems.”
Zhang is the James and Patricia Poitras Professor of Neuroscience at MIT, an associate professor in the MIT 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.
The MIT Media Lab, Broad Institute of MIT and Harvard, and MIT departments of Brain and Cognitive Sciences and Biological Engineering contributed to this article.
Feng Zhang elected to National Academy of Sciences
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
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
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
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
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.