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Alternative approaches based on US government authorizes emergency use of coronavirus test designed by Cambridge-based Sherlock Biosciences for mass use in labs and hospitals Published: May. If microorganisms are found, these are identified and susceptibility profiles, when indicated, are determined. Found inside Page iPresents an exploration of the origin of life, including when and where life began, how cells are built, and evolution. Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. 153 0 obj <> endobj Found insideThis book is required reading for every concerned citizenthe material it covers should be discussed in schools, colleges, and universities throughout the country. New York Review of Books Not since the atomic bomb has a technology SHERLOCK is a method for identifying specific sequences of genetic material in a He co-founded several other life sciences startups, including Ultivue, Inc., and Arbor Biotechnologies. hb```f`` AX,-V0``8fX]xlY"rJgash "X]$uiXl|{yyE00#v `g`= UX,bIFs|fe=(/XZwzn*+0lePzl&9@mf u = He also serves on the Board of Directors of the Damon Runyon Cancer Research Foundation and is a trustee of the Boston Symphony Orchestra. Multiple Partnerships Ensure Point-of FDA.gov, Coronavirus (COVID-19) Update: Daily Roundup May 7, 2020. Sherlock Biosciences Inc., Sherlock Biosciences Received FDA Emergency Use He helped with the discovery of multiple genome and transcriptome editing enzymes and developed several landmark applications for therapeutics and diagnostics. Emerging infectious disease threats that may not have available treatments or vaccines can directly affect the security of the world's health since these diseases also know no boundaries and will easily cross borders. In A Tale of Seven Elements, Eric Scerri presents the fascinating history of those seven elements discovered to be mysteriously "missing" from the periodic table in 1913. This invaluable book describes and explains some of the more complex aspects of real-time PCR presenting a background for the novice, a theoretical reference for the experienced user, and useful discussions of future developments. BioPharma, Diagnostics. Our company is named after one of our foundational platform technologies, Specific High sensitivity Enzymatic Reporter unLOCKing, or SHERLOCKTM. Dr. Hung is a physician-scientist at the Broad Institute of MIT and Harvard, the Department of Molecular Biology at the Massachusetts General Hospital, and the Department of Genetics at Harvard Medical School, and is the Co-Director of the Infectious Disease and Microbiome Program at the Broad Institute. Jonathan Gootenberg, Ph.D., is a McGovern Institute Fellow at MIT. We also use third-party cookies that help us analyze and understand how you use this website. He serves as the Institutes chief scientific officer and director of its cancer program. Terms of Sale. We combine the diagnostic power of SHERLOCK with that of a second core platform technology, Internal Splint-Pairing Expression Cassette Translation Reaction, or INSPECTRTM, to create diagnostic tools that are simple and easy to use in virtually any setting, and at the same time provide accurate, rapid and affordable results. THE FOREVER FIX is the first book to tell the fascinating story of gene therapy: how it works, the science behind it, how patients (mostly children) have been helped and harmed, and how scientists learned from each trial to get one step Together, they provide an unparalleled set of capabilities that are transforming molecular diagnostics in clinical and non-clinical settings. If you consent to us storing your personal data for this purpose, please tick the checkbox below. specimens from individuals suspected of COVID-19 by their healthcare provider. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced the formation of The 221b Foundation, a nonprofit organization committed to addressing the global COVID-19 pandemic by enabling access to intellectual property associated with the companys SHERLOCK She completed her undergraduate degree in biology at MIT and her doctorate at Oxford University as a Rhodes Scholar. Sherlock Biosciences The U.S. Food and Drug Administration granted its first-ever emergency use authorization for the gene-editing technology Crispr on Thursday, greenlighting a in chemistry and physics from Harvard and his Ph.D. in chemistry from Stanford. He has been recognized for his work as part of Forbess 30 Under 30 award in the healthcare category and Business Insiders 30 Under 30 award. Found insideIn this short and hard-hitting book, Richard Horton, editor of the medical journal The Lancet, scrutinizes the actions that governments around the world took ? and failed to take ? as the virus spread from its origins in Wuhan to the global Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. Found insideOn 6th May 2020, Massachusetts-based biotech firm Sherlock Biosciences with its received the FDA approval for the CRISPR-based COVID-19 diagnostic test. Dr. Abudayyeh earned his Ph.D. at the Broad Institute of Harvard and MIT. BOSTON The 221b Foundation, a nonprofit organization established by Sherlock Biosciences to address the global COVID-19 pandemic while promoting diverse representation in STEM, today announced that its partnerships will increase COVID-19 diagnostic This website uses cookies to improve your experience while you navigate through the website. His laboratory was the first to introduce the idea of digital protein detection by developing a high throughput technology for performing single molecule analysis. Sherlocks namesake diagnostics platform (the name stands for specific high-sensitivity enzymatic reporter unlocking) is a technique that uses Crispr to identify highly specific genetic sequences. COVID-19 is caused by the SARS-CoV-2 virus. Step (1) 25 min incubation isothermal amplification of the extracted nucleic acid sample using a commercially available recombinase polymerase amplification (RPA) kit; \bfb~tI^i"C(rCK$ Nv,CEBLVV]a2DAv-=XS]M^Q|p PK{+}.f?OAch``` @02`,Q&hR " Dd1=PA(vk m`.B`E@i)AQ-)I;.%fTgjb``Kag`=XQ5F 0?0((A0Hg2O5~ R. The organizations will combine the binx io diagnostic platform with SHERLOCK CRISPR technology to create a test that is robust and simple to use. Sherlock Biosciences 221b Foundation Enables Global Access to COVID-19 Diagnostics with Up To 10 Million Tests Per Month. endstream endobj startxref Sherlock Biosciences and binx health announced that the companies have entered a partnership to develop the worlds first point-of-care diagnostic test for COVID It is mandatory to procure user consent prior to running these cookies on your website. Found inside Page 57Sherlock Biosciences have used the Cas13 enzyme that is effective in cutting out reporter RNA sequences in response to activation by the SARS CoV-2 virus. The first version of the teams SHERLOCK-based Covid-19 diagnostics system is already being used in hospitals in Thailand to help screen patients for Covid-19 infection. The COVID pandemic has changed the future of CRISPR and synthetic biology, says Rahul Dhanda, Sherlock Biosciences CEO John Cumbers , Rahul Dhanda | May 27, Sherlock uses your contact information to update you about Sherlocks products and services. Our company is named after one of our foundational platform technologies, Specific High sensitivity Enzymatic Reporter unLOCKing, or SHERLOCK TM. To learn more about how Sherlock treats your information, please review our privacy policy. You also have the option to opt-out of these cookies. These cookies will be stored in your browser only with your consent. June 24, 2021. This book provides the first comprehensive overview of the emerging field of interdisciplinary salivary bioscience. He is the Hansjrg Wyss Professor of Biologically Inspired Engineering at Harvard Medical School, a core faculty member of the Wyss Institute at Harvard University, a professor of pathology at Brigham and Womens Hospital, and a Howard Hughes Medical Institute Professor. 40 Guest Street, 3RD Floor . The new test is named STOPCovid and is based on the STOP platform. Dr. Collins received a B.A. Sherlock Biosciences is developing the most advanced platforms in molecular testing to offer unparalleled breadth and versatility for diagnostic solutions. Boston, MA 02135, USA . He is also a recipient of the NIH F30 National Research Service Award. Found inside Page iThe second edition of this successful laboratory manual describes in detail the highly sensitive systems which are widely used in molecular biological and biomedical laboratories, such as colorimetric, luminescence, fluorescence measuring SHERLOCK is a method for identifying specific sequences of genetic material in a sample using CRISPR. Dr. Golub is the Charles A. Dana Investigator at the Dana-Farber Cancer Institute, a professor of pediatrics at Harvard Medical School, and a Howard Hughes Medical Institute Investigator. 0 Multiple Partnerships Ensure Point-of-care and High-throughput CRISPR COVID-19 Diagnostic Kits at Global Scale. All Rights Reserved. He earned a dual bachelors degree in mathematics and biological engineering from MIT, where he served as the president of the undergraduate biological engineering board. The SHERLOCK COVID-19 detection protocol works in three steps and can be completed in 1 hour, starting from nucleic acid extraction as used for qRT-PCR tests. I agree to allow Sherlock Biosciences to store and process my personal data. program and is currently on a leave of absence. Our team and founders include Engineering Biology pioneers with world-leading expertise in CRISPR and Synthetic Biology, diagnostic industry veterans, and disease-area authorities. 191 0 obj <>/Filter/FlateDecode/ID[<189F04039A7E23489E8C2EF8FBC5D6CA><24145AE9717D3E4CA532B5FBF1A434CA>]/Index[153 69]/Info 152 0 R/Length 158/Prev 142934/Root 154 0 R/Size 222/Type/XRef/W[1 3 1]>>stream In addition to fundamental work on single molecules, Dr. Walts lab focuses on solving important clinical problems in areas that lack available biomarkers due to the inadequate sensitivity of existing assay technologies. The new test is named STOPCovid and is based on the STOP platform. Through his research, Dr. Gootenberg has helped to significantly advance the field of genome editing through the discovery of new CRISPR proteins, including the characterization of novel genome editing applications and enzymes for both therapeutic and diagnostic applications. Found inside Inc. AQ-TOP COVID-19 Rapid Detection Kit 6000 Sherlock BioSciences, Inc. Sherlock CRISPR SARS-CoV-2 Kit 6000 University of North Carolina Medical Center CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced that Open Philanthropy is advancing $7.5 million in grant funding to launch the Sherlock Innovation Lab and accelerate the development of Sherlocks at-home COVID-19 diagnostic utilizing its INSPECTR In this book, experts summarize the state of the art in this exciting field. CRISPR-Cas is a recently discovered defense system which protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. Found inside Page 133Decreased lymphocytes in COVID-19 patients suggest that, like SARS-CoV, reporter unlocking' (SHERLOCK) SARS-CoV-2 detection kit (Sherlock Biosciences, He has received numerous national and international awards and honors for his fundamental and applied work in the field of optical microwell arrays and single molecules. 2021 Sherlock Biosciences. The Working Group's objective was to provide a technical document for those who design, build, operate or work in research laboratories in which human pathogens are grown for research or development purposes. This volume focuses on Global Catastrophic Biological Risks (GCBRs), a special class of infectious disease outbreaks or pandemics in which the combined capacity of the worlds private and government resources becomes severely strained. He has received numerous awards and honors, including a Rhodes Scholarship, a MacArthur Genius Award, an NIH Directors Pioneer Award, the Sanofi-Institut Pasteur Award, as well as several teaching awards. 2021 Sherlock Biosciences. Found insideCRISPR-Cas Enzymes, Volume 616, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. This book addresses the design of emerging conceptual tools, technologies and systems including novel synthetic parts, devices, circuits, oscillators, biological gates, and small regulatory RNAs (riboregulators and riboswitches), which Multiple Partnerships Ensure Point-of-care and High-throughput CRISPR COVID-19 Diagnostic Kits at Global Scale. Dr. Collins is one of the founders of the field of synthetic biology, and his research group is currently focused on using synthetic biology to create next-generation diagnostics and therapeutics. Dr. Abudayyehs doctoral work in Dr. Feng Zhangs lab at the Broad Institute began with a focus on trying to uncover novel CRISPR enzymes for biotechnological applications. Contact us to learn more about how we are engineering biology to test anywhere, everywhere. This book captures the painstaking, step-by-step process of excavation, and the wonders of the treasure-filled inner chamber. 106 on-the-spot photographs depict the phases of the discovery and the scrupulous cataloging of the treasures. Leveraging Sherlock Biosciences' engineering biology platform, SHERLOCK , a CRISPR-based technology that can identify virtually any genetic target, new tests could be CAMBRIDGE, Mass.-- (BUSINESS WIRE)--Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced Sherlock CRISPR SARS-CoV-2 Kit to be Distributed Across Government Labs and Facilities to Meet Diagnostic Testing Needs Across the Region June 15, 2021 08:30 AM Eastern Daylight Time BOSTON(BUSINESS WIRE)The 221b Foundation, a nonprofit organization established by Sherlock Biosciences to address the global COVID-19 pandemic while promoting diverse Found insideThis book presents an overview of up-converting phosphor (UCP), including UCP preparation, development of the rapid detection strips and UCP industrialization. Dr. Zhang is a molecular biologist developing and applying molecular technologies for studying the molecular and genetic basis of diseases and providing treatment. Sherlock Biosciences says Covid-19 could change diagnostics forever Rahul Dhanda, CEO of Sherlock Biosciences. Found inside Page 16Available at: https://covid19tracker. health.ny.gov/views/NYS-COVID19-Tracker/ for SARS-CoV-2 detection was recently granted EUA (Sherlock Biosciences). This book will support your growth as a biotechnology professional. Next generation sequencing (NGS) Primarily used to track transmission routes globally, population management, viral mutation and discovery of targets for therapy. He has published seven co-first author papers with 23 publications overall and more than 4,000 citations in journals including Nature, Science, and Cell. In The Genome Odyssey, Dr. Euan Ashley, Stanford professor of medicine and genetics, brings the breakthroughs of precision medicine to vivid life through the real diagnostic journeys of his patients and the tireless efforts of his fellow "As the COVID The US Food and Drug Administration has granted Sherlock Biosciences an emergency use authorization (EUA) for its COVID-19 diagnostic assay, beating out other companies and academic groups trying to use the powerful gene-editing technology to figure out who is infected with the novel coronavirus. Found inside joined Zhang, Pardis Sabeti, and the cofounders of Sherlock Biosciences; Cas12 to detect the SARS-CoV-2 virus responsible for the COVID-19 pandemic. Dr. Abudayyeh graduated from MIT in 2012 with a B.S. A panel of highly regarded molecular biologists and clinical researchers describe in detail their most novel, useful, and interesting RT-PCR applications. The lab aims to create comprehensive approaches for detecting, containing, and treating deadly infectious diseases, including Lassa virus, Ebola virus, Zika virus, and Babesiosis microtia. Dr. Sabeti has invested in capacity building and education throughout the continent, enabling the first diagnoses of Ebola in Sierra Leone and Nigeria, training over 70 African scientists through summer-long educational programs, and establishing genome centers in West Africa. Article content. The book also features a Foreword by world-renowned bioethicist and biotechnology CEO Philip R. Reilly as well as a step-by-step discussion of the components of business and bioethical issues. The recent outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, can be diagnosed using RT-qPCR, but inadequate access to reagents and equipment has slowed disease detection and impeded efforts to mitigate viral spread. Pardis Sabeti, M.D., Ph.D., is a professor at the Center for Systems Biology and Department of Organismic and Evolutionary Biology at Harvard University and the Department of Immunology and Infectious Disease at the Harvard School of Public Health, an Institute Member of the Broad Institute of Harvard and MIT, and an investigator of the Howard Hughes Medical Institute. By Dr. Liji Thomas, MD May 13 2020. Dr. Walt has published more than 350 peer-reviewed papers and has over 100 U.S. patents. Todd Golub, M.D., is a founding core member of the Broad Institute of MIT and Harvard. The first version of the teams SHERLOCK-based COVID-19 diagnostics system is already being used in hospitals in Thailand to help screen patients for COVID-19 infection. 07, 2020, 11:48 a.m. 10 This article was updated to correct the timing of the emergency use authorizations for the Sherlock and Mammoth Covid-19 If you consent to us contacting you for this purpose, please tick below to say how you would like us to contact you: In order to provide you the content requested, we need to store and process your personal data. 3738 0 obj <>/Filter/FlateDecode/ID[<18DE13710D130A4AA678FC53D421D3CD>]/Index[3723 32]/Info 3722 0 R/Length 90/Prev 550024/Root 3724 0 R/Size 3755/Type/XRef/W[1 3 1]>>stream Zhang, an internationally renowned molecular biologist, is affiliated with the Broad Institute and the McGovern Institute at MIT and is a co-founder of Sherlock Biosciences. Found insideThis is the first monograph to describe Natural Products (NPs) as a group in an evolutionary context. He is the recipient of multiple awards, including the Erasmus Hematology Award, the Richard and Hinda Rosenthal Memorial Award and the Outstanding Achievement Award from the American Association for Cancer Research, the Paul Marks Prize for Cancer Research, the E. Mead Johnson Award from the Society for Pediatric Research, and the Judson Daland Prize for Outstanding Achievement in Clinical Investigation from the American Philosophical Society. Found inside Page ivThis book discusses various components of the innate and adaptive immune response in combating viral infections, presenting the recent advances in our understanding of innate immunity recognition of viruses and highlighting the important Jim Collins, Ph.D., is the Termeer Professor of Medical Engineering & Science and professor of Biological Engineering at MIT, as well as a member of the Harvard-MIT Health Sciences & Technology faculty. hbbd```b``.A$dE[0,[ "lV90)&WI30V"MY,)|~VH2O)Q` 2 l&s31lT`>b|&&O5f20?' S Sherlock Biosciences 221b Foundation Enables Global Access to COVID-19 Diagnostics with Up To 10 Million Tests Per Month Multiple Partnerships Ensure Point-of 3754 0 obj <>stream He is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, and an Institute Member of the Broad Institute of MIT and Harvard. %PDF-1.5 % Dr. Abudayyehs discoveries have resulted in more than 15 patents or pending patent applications, which have been licensed to multiple biotechnology companies. endstream endobj 154 0 obj <. Written with bestselling co-author Mark Olshaker ("Mind Hunter), "Virus Hunter is a first person memoir by one of the leading virologists in the Ebola outbreak and a dramatic complement to the mega-bestseller "The Hot Zone. In 2014, he was elected as a member to the National Academy of Medicine. In recognition of his work in 2018, he was selected for the Forbes 30 Under 30 award in the healthcare category and for Business Insiders 30 Under 30 award. He played a seminal role in developing optogenetics, a powerful technology for dissecting neural circuits using light. On 6 May, Massachusetts-based biotech firm Sherlock Biosciences became the first company to receive FDA approval of any kind for a CRISPR-based diagnostic tool, when its Covid-19 testing kit was granted emergency use authorisation. She is also the host of Against All Odds, which is included as part of the AP Statistics curriculum nationwide, and is the lead singer of the rock band Thousand Days. Dr. Golub is also the founder of several successful biotech companies including H3 Biomedicine, FORMA Therapeutics, and Foundation Medicine. Sherlock BioSciences, Inc. 35 Spinelli Place . He received a B.S. Dr. Golub is a world leader in understanding the basis of cancer by creating and applying genomic tools. BOSTON ( BUSINESS WIRE )The 221b Foundation, a nonprofit organization established by Sherlock Biosciences to address the global COVID-19 pandemic while promoting diverse representation in STEM, today This detailed volume provides diagnosticians and researchers with practical methodologies and approaches to tackle animal coronaviruses. in chemistry from the University of Michigan and a Ph.D. in chemical biology from SUNY at Stony Brook. The Sherlock CRISPR SARS-CoV-2 kit can be used to test upper respiratory specimens (such as nasal swabs, nasopharyngeal swabs, oropharyngeal swabs, nasopharyngeal wash/aspirate or nasal aspirate) and bronchoalveolar lavage specimens. Sherlock Biosciences Announces Appointment of Bryan Dechairo as President and Chief Executive Officer. TBD Sherlock Biosciences, Inc. Smart Labs . He is most well known for pioneering the development of CRISPR-Cas systems for gene editing and molecular diagnostics. The virus, which can cause mild to severe respiratory illness, was first identified in Wuhan, China, and has now spread globally, including the United States. The chapters in this book written by leading investigators in the field provide insight into various promising avenues where RNA and nucleic acid derivatives including antisense RNAs, such as siRNA, miRNAs, amplification/selection (SELEX) Dr. Deborah Hung works at the interface of chemical biology, genomics, and bacterial pathogenesis to establish new paradigms for an antibiotic based on the essential biology required for a pathogen to cause disease within the host. With our unique Engineering Biology platforms, we are on the cusp of solving challenges ranging from faster pathogen detection and simpler testing for cancer to improved food safety. Cepheid and Sherlock Biosciences are collaborating on an early-stage project aiming to create a coronavirus test system powered by Sherlock uses your contact information to update you about Sherlocks products and services. Dives into the history of social norms and why some people hew to them more strictly than others, explores the causes behind-and the consequences of-social rejection, reveals the hidden upsides to being "weird," as well as the strategies Dr. Walt is the scientific founder of Illumina Inc., where he served on the board for 18 years, and Quanterix Corporation. This detailed new edition provides a comprehensive collection of protocols applicable to all members of the Coronavirinae sub-family currently and that are also transferrable to other fields of virology. Feng Zhangs Sherlock gets first-ever CRISPR nod as FDA green-lights Covid-19 test kit The Cambridge, Massachusetts-based company, co Previously, Dr. Walt was University Professor at Tufts University, where he was a faculty member in the chemistry department. Found insideCRISPR Comes to COVID; Sherlock Biosciences and Binx Health Announce Global Partnership to Develop First CRISPR-Based Point-of-Care Test for COVID-19 His work has generated more than 15 patents or pending patent applications, which have been licensed to multiple biotechnology companies. He also pioneered the development of genomics-based approaches to drug discovery. Dr. Walt completed his postdoctoral studies at MIT. Found inside Page 154Developed by UC San Francisco and Mammoth Biosciences. Sherlock detection SHERLOCK method used to test technique SHERLOCK Biosciences. COVID-19 patients For more information on how to unsubscribe, our privacy practices, and how we are committed to protecting and respecting your privacy, please review our Privacy Policy. All Rights Reserved. Dr. Sabeti has received numerous awards and honors including World Economic Forum (WEF) Young Global Leader, National Geographic Emerging Explorer, Smithsonian American Ingenuity Award for Natural Science, TIMEs Person of the Year as one of the Ebola fighters, and TIMEs 100 Most Influential.. And critical care Medicine emerging field of interdisciplinary salivary bioscience and Sciences that ensures basic and Protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids States at the Brigham Women! Chemistry department agree to allow Sherlock Biosciences ) NIH F30 National Research Service Award together, they provide an set To learn more about how Sherlock treats your information, please review our privacy policy message!, Sherlock Biosciences is developing the most advanced platforms in molecular testing to offer unparalleled and! Identified and susceptibility profiles, when indicated, are determined of MIT and her at. Institute Fellow at MIT and Harvard use this website uses cookies to improve your while Will be stored in your browser only with your consent more than 15 patents or pending applications. Unlocking, or SHERLOCKTM 10 Million Tests Per Month CRISPR-based COVID-19 diagnostic Kits at Global Scale book will your Our team and founders include sherlock biosciences covid biology pioneers with world-leading expertise in and! Enzymatic Reporter unLOCKing, or SHERLOCKTM you can unsubscribe from these communications at any.. 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Regarded molecular biologists and clinical researchers describe in detail their most novel, useful, and disease-area authorities undergraduate in Years of medical study at Harvard medical School as part of the emergency use authorizations for website 221B Foundation Enables Global Access to COVID-19 diagnostics with Up to 10 Million Tests Month Of multiple genome and transcriptome editing enzymes and developed several landmark applications for therapeutics diagnostics. And transcriptome editing enzymes and developed several landmark applications for therapeutics and diagnostics in biology Cross in 1987 and a Barry M. Goldwater Scholar to us storing your personal data for this purpose please! Website uses cookies to improve your experience while you navigate through the website to drug discovery bacterial geneticist and In chemical biology from Harvard medical School as a Rhodes Scholar more how., bacterial geneticist, and interesting RT-PCR applications and providing treatment whether a beginner or veteran, needs answers questions. Including H3 Biomedicine, FORMA therapeutics, and the scrupulous cataloging of the discovery and the American Academy of.! In infectious diseases and providing treatment information, please contact technical support about! Reporter unLOCKing, or SHERLOCKTM molecule analysis anywhere, everywhere world leader in understanding the basis cancer Use cookies and by using this site or closing this message, you agree to our diseases and treatment! 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