Publication Date:
2019
Description:
〈p〉Although Cas9-mediated genome editing has been widely used to engineer alleles in animal models of human inherited diseases, very few homology-directed repair (HDR)–based genetic editing systems have been established in postnatal mouse models for effective and lasting phenotypic rescue. Here, we developed an HDR-based Cas9/RecA system to precisely correct 〈i〉Pde6b〈/i〉 mutation with increased HDR efficiency in postnatal 〈i〉rodless〈/i〉 (〈i〉rd1〈/i〉) mice, a retinitis pigmentosa (RP) mutant model characterized by photoreceptor degeneration and loss of vision. The Cas9/RecA system incorporated Cas9 endonuclease enzyme to generate double-strand breaks (DSBs) and bacterial recombinase A (RecA) to increase homologous recombination. Our data revealed that Cas9/RecA treatment significantly promoted the survival of both rod and cone photoreceptors, restored the expression of PDE6B in rod photoreceptors, and enhanced the visual functions of 〈i〉rd1〈/i〉 mice. Thus, this study provides a precise therapeutic strategy for RP and other genetic diseases.〈/p〉
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General
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