CRISPR/Cas9 mediated somatic gene therapy for insertional mutations: the vibrator mouse model.

ABSTRACT: Somatic gene therapy remains technically challenging, especially in the central nervous system (CNS). Efficiency of gene delivery, efficacy in recipient cells, and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic approach. Recent efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant mutations. Here we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation, vibrator (vb), in the mouse brain. The vb mice expressed ∼20% of normal levels of phosphatidylinositol transfer protein, α (PITPα) RNA and protein due to an endogenous retrovirus inserted in intron 4, resulting in early-onset tremor, deg

SUBMITTER: Fu X 

PROVIDER: S-EPMC8982555 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature