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CRISPR-Cas9 knockin mice for genome editing and cancer modeling.
Platt, Randall J; Chen, Sidi; Zhou, Yang; Yim, Michael J; Swiech, Lukasz; Kempton, Hannah R; Dahlman, James E; Parnas, Oren; Eisenhaure, Thomas M; Jovanovic, Marko; Graham, Daniel B; Jhunjhunwala, Siddharth; Heidenreich, Matthias; Xavier, Ramnik J; Langer, Robert; Anderson, Daniel G; Hacohen, Nir; Regev, Aviv; Feng, Guoping; Sharp, Phillip A; Zhang, Feng.
Afiliación
  • Platt RJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological
  • Chen S; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zhou Y; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Yim MJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological
  • Swiech L; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological
  • Kempton HR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Dahlman JE; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachuse
  • Parnas O; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Eisenhaure TM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Jovanovic M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Graham DB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jhunjhunwala S; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Heidenreich M; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological
  • Xavier RJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Langer R; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachuse
  • Anderson DG; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachuse
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Feng G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Stanley Center for Psychi
  • Sharp PA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sharppa@mit.edu.
  • Zhang F; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological
Cell ; 159(2): 440-55, 2014 Oct 09.
Article en En | MEDLINE | ID: mdl-25263330
ABSTRACT
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(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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Oncogenes / Adenocarcinoma / Ingeniería Genética / Genes Supresores de Tumor / Modelos Animales de Enfermedad / Neoplasias Pulmonares Límite: Animals Idioma: En Año: 2014 Tipo del documento: Article
Texto completo
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XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Oncogenes / Adenocarcinoma / Ingeniería Genética / Genes Supresores de Tumor / Modelos Animales de Enfermedad / Neoplasias Pulmonares Límite: Animals Idioma: En Año: 2014 Tipo del documento: Article