CRISPR-Cas9 knockin mice for genome editing and cancer modeling

Randall J. Platt, Sidi Chen, Yang Zhou, Michael J. Yim, Lukasz Swiech, Hannah R. Kempton, James E. Dahlman, Oren Parnas, Thomas M. Eisenhaure, Marko Jovanovic, Daniel B. Graham, Siddharth Jhunjhunwala, Matthias Heidenreich, Ramnik J. Xavier, Robert Langer, Daniel G. Anderson, Nir Hacohen, Aviv Regev, Guoping Feng, Phillip A. SharpFeng Zhang

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

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 KrasG12D 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.

اللغة الأصليةإنجليزيّة أمريكيّة
الصفحات (من إلى)440-455
عدد الصفحات16
دوريةCell
مستوى الصوت159
رقم الإصدار2
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 9 أكتوبر 2014
منشور خارجيًانعم

All Science Journal Classification (ASJC) codes

  • !!General Biochemistry, Genetics and Molecular Biology

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