Mutant huntingtin messenger RNA (mHTT mRNA) (mHTT mRNA)

Mutant huntingtin (mHTT) RNA transcripts are the messenger RNA products of the HTT gene containing an abnormally expanded CAG trinucleotide repeat (UniProt P42858). These transcripts serve as the template for the synthesis of the mutant huntingtin protein, which is the primary driver of Huntington's disease (HD), a progressive neurodegenerative disorder (Tabrizi et al., NEJM 2019). Beyond their role in protein synthesis, the expanded RNA transcripts themselves may contribute to pathogenesis through RNA-mediated toxicity, such as sequestering RNA-binding proteins (Vugter et al., 2020). Therapeutic strategies targeting mHTT RNA aim to reduce the levels of toxic protein by promoting RNA degradation via antisense oligonucleotides (ASOs) like Tominersen or RNA interference (RNAi) like AMT-130 (uniQure, 2024). Other approaches include small molecule splicing modulators like PTC518 that induce premature stop codons to prevent translation (PTC Therapeutics, 2024). A critical challenge in this field is achieving allele-specific knockdown to preserve the levels of wild-type huntingtin protein, which is essential for neuronal survival and function (Wave Life Sciences, 2024).

Other names

mHTT mRNAMutant HTT transcriptsCAG-expanded HTT mRNAHuntingtin messenger RNA

RNase H-mediated mRNA degradation, RNA interference (RNAi), and splicing modulation to induce premature termination codons.