CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
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)-, le...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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Other Authors: | |
Format: | Article |
Language: | en_US |
Published: |
Elsevier
2016
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Online Access: | http://hdl.handle.net/1721.1/101139 https://orcid.org/0000-0003-2782-2509 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0002-8021-277X https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0001-6683-5498 https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 |
Summary: | 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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