Mutant allele knockout with novel CRISPR nuclease promotes myelopoiesis in ELANE neutropenia.

ABSTRACT: Severe congenital neutropenia (SCN) is a life-threatening marrow failure disorder, usually caused by heterozygous mutations in ELANE. Potential genetic treatment strategies include biallelic knockout or gene correction via homology-directed repair (HDR). Such strategies, however, involve the potential loss of the essential function of the normal allele product or limited coverage of diverse monogenic mutations within the patient population, respectively. As an alternative, we have developed a novel CRISPR-based monoallelic knockout strategy that precisely targets the heterozygous sites of single-nucleotide polymorphisms (SNPs) associated with most ELANE mutated alleles. In vitro studies demonstrate that patients' unedited hematopoietic CD34⁺ cells have signi

SUBMITTER: Sabo P 

PROVIDER: S-EPMC9240714 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature