In Vivo Base Editing of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) as a Therapeutic Alternative to Genome Editing.

ABSTRACT:

Objective

High-efficiency genome editing to disrupt therapeutic target genes, such as PCSK9 (proprotein convertase subtilisin/kexin type 9), has been demonstrated in preclinical animal models, but there are safety concerns because of the unpredictable nature of cellular repair of double-strand breaks, as well as off-target mutagenesis. Moreover, precise knock-in of specific nucleotide changes-whether to introduce or to correct gene mutations-has proven to be inefficient in nonproliferating cells in vivo. Base editors comprising CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR-associated 9) fused to a cytosine deaminase domain can effect the alteration of cytosine bases to thymine bases in genomic DNA in a sequence-specific fashion, witho

SUBMITTER: Chadwick AC 

PROVIDER: S-EPMC5570639 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature