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Rapid in vivo multiplexed editing (RIME) of the adult mouse liver.


ABSTRACT:

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 .

SUBMITTER: Katsuda T 

PROVIDER: S-EPMC11088813 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Rapid in vivo multiplexed editing (RIME) of the adult mouse liver.

Katsuda Takeshi T   Katsuda Takeshi T   Cure Hector H   Sussman Jonathan J   Simeonov Kamen P KP   Krapp Christopher C   Arany Zoltan Z   Grompe Markus M   Stanger Ben Z BZ  

Hepatology (Baltimore, Md.) 20221013 2


<h4>Background and aims</h4>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.<h4>Approach and results</h4>RIME, a system wherein CRISPR/caspa  ...[more]

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