CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
By Randall J. Platt, Sidi Chen, Yang Zhou, Michael J. Yim, L. Swiech, Hannah R. Kempton, J. Dahlman, Oren Parnas, T. Eisenhaure, M. Jovanović and 10 more. Cell, 2014
1,875 citations recorded by the source corpus.
SUMMARY CRISPR-Cas9 is a versatile genome editing technology for studying the function 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)-, lenti-virus-, 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 KRASG12D mutations, leading to macroscopic tumors of adeno-carcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/5c3c7fed0c5472792e75fa7c4d4f66de6e4b979a
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Citations in the corpus
- Delivering CRISPR: a review of the challenges and approaches (2018, background): “This resulted in the generation of lung adenocarcinoma (Platt et al., 2014).”
- Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems (2016, background): “Other approaches are also being pursued, including nonviral methods for delivery of DNA or mRNA by nanoparticles (163) and electroporation (164), or direct delivery of Cas9 protein (165).”
- Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. (2016, methodology): “REAGENT or RESOURCE SOURCE IDENTIFIER Critical Commercial Assays 10x Chromium Single Cell 30 Kit 10X Genomics scRNA-seq Deposited Data Bam files This Paper GEO: GSE90063 Compiled gene expression matrices This Paper GEO: GSE90063 Experimental Models: Cell Lines K562 Cell Line Wang et al., 2015 K562 B”