Huntingtin messenger RNA (HTT mRNA) (HTT mRNA)

Huntingtin messenger RNA (HTT mRNA) is the transcript produced from the HTT gene, serving as the template for the synthesis of the huntingtin protein, which is critical for neuronal health and development (UniProt, 2024). In Huntington's disease (HD), an autosomal dominant neurodegenerative disorder, a CAG trinucleotide repeat expansion in the HTT gene results in a mutant mRNA that encodes a toxic protein with an expanded polyglutamine tract (NIH, 2023). This mutant protein (mHTT) aggregates and disrupts various cellular processes, leading to progressive neurodegeneration primarily in the striatum and cerebral cortex (PubMed, 2022). As a therapeutic target, HTT mRNA is prioritized because lowering its levels can prevent the production of the toxic protein at its source. Current drug development strategies include antisense oligonucleotides (ASOs) like Tominersen that trigger RNase H-mediated degradation, and gene therapies like AMT-130 that use RNA interference (RNAi) (Roche, 2021; uniQure, 2023). A major clinical challenge involves the balance of huntingtin lowering, where therapies must ideally reduce the mutant form while preserving enough wild-type huntingtin to maintain essential biological functions (Nature Reviews Neurology, 2020).

Other names

HTT transcriptHuntingtin mRNAHD mRNAIT15 mRNAHuntingtin gene transcript

Antisense oligonucleotide-mediated RNase H degradation, RNA interference (RNAi) via the RISC complex, and small molecule-mediated splicing modulation.