TY - JOUR
T1 - Rapid in vivo multiplexed editing (RIME) of the adult mouse liver
AU - Katsuda, Takeshi
AU - Cure, Hector
AU - Sussman, Jonathan
AU - Simeonov, Kamen P.
AU - Krapp, Christopher
AU - Arany, Zoltan
AU - Grompe, Markus
AU - Stanger, Ben Z.
N1 - Publisher Copyright:
© 2023 John Wiley and Sons Inc.. All rights reserved.
PY - 2023/8
Y1 - 2023/8
N2 - Background and Aims: Assessing mammalian gene function in vivo has traditionally relied on manipulation of the mouse genome in embryonic stem cells or perizygotic embryos. These approaches are time-consuming and require extensive breeding when simultaneous mutations in multiple genes is desired. The aim of this study is to introduce a rapid in vivo multiplexed editing (RIME) method and provide proof of concept of this system. Approach and Results: RIME, a system wherein CRISPR/caspase 9 technology, paired with adeno-associated viruses (AAVs), permits the inactivation of one or more genes in the adult mouse liver. The method is quick, requiring as little as 1 month from conceptualization to knockout, and highly efficient, enabling editing in >95% of target cells. To highlight its use, we used this system to inactivate, alone or in combination, genes with functions spanning metabolism, mitosis, mitochondrial maintenance, and cell proliferation. Conclusions: RIME enables the rapid, efficient, and inexpensive analysis of multiple genes in the mouse liver in vivo.
AB - Background and Aims: Assessing mammalian gene function in vivo has traditionally relied on manipulation of the mouse genome in embryonic stem cells or perizygotic embryos. These approaches are time-consuming and require extensive breeding when simultaneous mutations in multiple genes is desired. The aim of this study is to introduce a rapid in vivo multiplexed editing (RIME) method and provide proof of concept of this system. Approach and Results: RIME, a system wherein CRISPR/caspase 9 technology, paired with adeno-associated viruses (AAVs), permits the inactivation of one or more genes in the adult mouse liver. The method is quick, requiring as little as 1 month from conceptualization to knockout, and highly efficient, enabling editing in >95% of target cells. To highlight its use, we used this system to inactivate, alone or in combination, genes with functions spanning metabolism, mitosis, mitochondrial maintenance, and cell proliferation. Conclusions: RIME enables the rapid, efficient, and inexpensive analysis of multiple genes in the mouse liver in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85139663149&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139663149&partnerID=8YFLogxK
U2 - 10.1002/hep.32759
DO - 10.1002/hep.32759
M3 - Article
C2 - 36037289
AN - SCOPUS:85139663149
SN - 0270-9139
VL - 78
SP - 486
EP - 502
JO - Hepatology
JF - Hepatology
IS - 2
ER -