Limits of using oligonucleotides for allele-selective inhibition at trinucleotide repeat sequences - targeting the CAG repeat within ataxin-1.

ABSTRACT: Trinucleotide repeats are responsible for many genetic diseases. Previous studies have shown that duplex RNAs (dsRNAs) can be used to target expression of a mutant repeat allele while leaving expression of the wild-type allele untouched, creating opportunities for allele-selective inhibition and better therapeutic outcomes. In contrast to successes with other genes, we report here that we cannot achieve allele-selective inhibition when targeting the expanded CAG repeat within Ataxin-1 (ATXN1), the cause of spinal cerebellar ataxia-1 (SCA1). The most likely explanation for this unfavorable outcome is that the mean CAG repeat number within wild-type ATXN1 is relatively high compared to other trinucleotide repeat diseases. Because the wild-type repeat number is high, it is likely that there i

SUBMITTER: Hu J 

PROVIDER: S-EPMC7174099 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature