Genome writing and Targeted Delivery of the <i>NKX6-3/ANK1</i> gene cluster and its Type 2 Diabetes GWAS Variants to Human iPSCs.

ABSTRACT: Genome-wide association studies (GWAS) identified over 600 loci containing single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), most of which reside in non-coding regions. Among the set of T2D SNPs, linking causal genome variants to disease risk experimentally has remained a challenge; however, advances in synthetic mammalian genome writing techniques now enable the delivery of multiple haplotypes to human induced pluripotent stem cells (hiPSCs) to create a series of isogenic cell lines that can be differentiated and phenotyped in vitro. Here, to begin efforts in dissecting a T2D GWAS locus, we engineered an NKX6-3/ANK1 gene cluster knockout hiPSC line and introduced a landing pad facilitating the delivery of synthetic haplotype payloads. We built fou

SUBMITTER: Chalhoub N 

PROVIDER: S-EPMC12776320 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature