antisense oligonucleotide targeting rs7685686

This antisense oligonucleotide (ASO) is an experimental, allele-specific therapeutic designed for the treatment of Huntington's disease (HD). It specifically targets the rs7685686 single nucleotide polymorphism (SNP) within the huntingtin (HTT) gene. By selectively binding to the mutant HTT allele (typically the 'A' variant), the ASO triggers RNase H-mediated degradation of the mutant mRNA, thereby reducing the levels of the toxic mutant huntingtin protein while sparing the wild-type protein. The lead candidates, such as A38 and A39, utilize a mixmer design incorporating 2'-O-methoxyethyl (MOE) and constrained ethyl (cEt) modifications to optimize potency, stability, and allele-selectivity. Preclinical studies in patient-derived fibroblasts and transgenic mouse models (YAC18 and BACHD) have demonstrated significant reduction of mutant HTT with high specificity, suggesting a potential therapeutic benefit for a large majority of HD patients who carry this SNP.

Other names

HTT-rs7685686 ASOHTT-rs-7685686 ASOHTT-rs 7685686 ASOrs7685686-targeted ASOrs-7685686-targeted ASOrs 7685686-targeted ASOallele-specific HTT ASO targeting rs7685686