Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.

ABSTRACT:

Abstract

Treatment options for the bleeding disorder von Willebrand disease type 2B (VWD2B) are insufficient and fail to address the negative effects of circulating mutant von Willebrand factor (VWF). The dominant-negative nature of VWD2B makes functionally defective VWF an interesting therapeutic target. Previous in vitro studies have demonstrated the feasibility of allele-selective silencing of mutant VWF using small interfering RNAs (siRNAs) targeting common single nucleotide polymorphisms (SNPs) in the human VWF gene, an approach that can be applied irrespective of the disease-causing VWF mutation. This study aims to extend this concept to a heterozygous VWD2B mouse model (c.3946G>A; p.Val1316Met) here using mouse strain-specific genetic differences as proxy for human SNPs. Hom

SUBMITTER: Linthorst NA 

PROVIDER: S-EPMC11786658 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature