A framework for individualized splice-switching oligonucleotide therapy.

ABSTRACT: Splice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases¹, but the systematic identification of such individuals remains a challenge. Here we performed whole-genome sequencing analyses to characterize genetic variation in 235 individuals (from 209 families) with ataxia-telangiectasia, a severely debilitating and life-threatening recessive genetic disorder^2,3, yielding a complete molecular diagnosis in almost all individuals. We developed a predictive taxonomy to assess the amenability of each individual to splice-switching ASO intervention; 9% and 6% of the individuals had variants that were 'probably' or 'possibly' amenable to ASO splice modulation, respectively. Most amenable variants were in deep intron

SUBMITTER: Kim J 

PROVIDER: S-EPMC10371869 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature