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|a dc
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|a Chen, Sidi
|e author
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|a Massachusetts Institute of Technology. Institute for Medical Engineering & Science
|e contributor
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|a Harvard University-
|e contributor
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|a Massachusetts Institute of Technology. Department of Biological Engineering
|e contributor
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|a Massachusetts Institute of Technology. Department of Biology
|e contributor
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|a Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
|e contributor
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|a Massachusetts Institute of Technology. Department of Chemical Engineering
|e contributor
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|a McGovern Institute for Brain Research at MIT
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Platt, Randall
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|a Chen, Sidi
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|a Zhou, Yang
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|a Yim, Michael J.
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|a Swiech, Lukasz
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|a Kempton, Hannah R.
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|a Dahlman, James E.
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|a Jhunjhunwala, Siddharth
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|a Heidenreich, Matthias
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|a Langer, Robert
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|a Anderson, Daniel Griffith
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|a Regev, Aviv
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|a Feng, Guoping
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|a Sharp, Phillip A.
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|a Zhang, Feng
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|a Zhou, Yang
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|a Yim, Michael J.
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|a Swiech, Lukasz
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|a Kempton, Hannah R.
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|a Dahlman, James E.
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|a Parnas, Oren
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|a Eisenhaure, Thomas M.
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|a Jovanovic, Marko
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|a Graham, Daniel B.
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|a Jhunjhunwala, Siddharth
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|a Heidenreich, Matthias
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|a Xavier, Ramnik J.
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|a Hacohen, Nir
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|a Regev, Aviv
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|a Feng, Guoping
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|a Sharp, Phillip A.
|e author
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|a Zhang, Feng
|e author
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|a Anderson, Daniel Griffith
|e author
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|a Kempton, Hannah R.
|e author
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|a Dahlman, James E.
|e author
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|a Sharp, Phillip A.
|e author
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|a Langer, Robert S
|e author
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|a Platt, Randall Jeffrey
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|a Yim, Michael
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|a CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
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| 260 |
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|b Elsevier,
|c 2016-02-09T18:37:24Z.
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| 856 |
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|z Get fulltext
|u http://hdl.handle.net/1721.1/101139
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|a CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras[superscript G12D] mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
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|a National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374)
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| 520 |
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|a Damon Runyon Cancer Research Foundation (Fellowship DRG-2117-12)
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| 520 |
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|a Massachusetts Institute of Technology. Simons Center for the Social Brain (Postdoctoral Fellowship)
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| 520 |
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|a European Molecular Biology Organization (Fellowship)
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| 520 |
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|a Foundation for Polish Science (Fellowship)
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| 520 |
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|a American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship
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| 520 |
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|a National Science Foundation (U.S.). Graduate Research Fellowship
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| 520 |
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|a Massachusetts Institute of Technology (Presidential Graduate Fellowship)
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| 520 |
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|a Human Frontier Science Program (Strasbourg, France) (Postdoctoral Fellowship)
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| 520 |
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|a National Human Genome Research Institute (U.S.) (CEGS P50 HG006193)
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|a Howard Hughes Medical Institute
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| 520 |
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|a Klarman Cell Observatory
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| 520 |
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|a National Cancer Institute (U.S.) (Center of Cancer Nanotechnology Excellence Grant U54CA151884)
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|a National Institutes of Health (U.S.) (Controlled Release Grant EB000244)
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|a National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology (PEN) Award Contract HHSN268201000045C)
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| 520 |
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|a Massachusetts Institute of Technology (Poitras Gift 1631119)
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| 520 |
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|a Stanley Center
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| 520 |
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|a Simons Foundation (6927482)
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|a Nancy Lurie Marks Family Foundation (6928117)
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| 520 |
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|a United States. Public Health Service (National Institutes of Health (U.S.) R01-CA133404)
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|a David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)
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| 520 |
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|a MIT Skoltech Initiative
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| 520 |
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|a National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)
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| 520 |
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|a National Institute of Mental Health (U.S.) (Director's Pioneer Award DP1-MH100706)
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| 520 |
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|a National Institute of Neurological Disorders and Stroke (U.S.) (Transformative R01 Grant R01-NS 07312401)
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| 520 |
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|a National Science Foundation (U.S.) (Waterman Award)
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| 520 |
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|a W. M. Keck Foundation
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| 520 |
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|a Kinship Foundation. Searle Scholars Program
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| 520 |
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|a Klingenstein Foundation
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| 520 |
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|a Vallee Foundation
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| 520 |
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|a Merkin Foundation
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|a en_US
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|a Article
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|t Cell
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