Human huntingtin messenger RNA (HTT mRNA)

Human huntingtin messenger RNA (HTT mRNA) is the transcript produced from the HTT gene, which in Huntington's disease (HD) contains an abnormally expanded CAG trinucleotide repeat. This expansion leads to the production of a mutant huntingtin (mHTT) protein that is prone to misfolding and aggregation, causing progressive neurodegeneration primarily in the striatum and cortex. HTT mRNA itself may also contribute to pathogenesis through RNA-mediated toxicity, such as the sequestration of splicing factors and the formation of toxic nuclear foci. As a therapeutic target, HTT mRNA is the focus of "huntingtin-lowering" strategies that aim to reduce the synthesis of the toxic protein by degrading the transcript or modulating its splicing. Current pharmacological approaches include antisense oligonucleotides (ASOs), RNA interference (RNAi) molecules like siRNAs and miRNAs, and small-molecule splicing modulators. While reducing mHTT is the primary goal, many therapies also lower wild-type huntingtin (wtHTT), raising concerns about the loss of its essential neuroprotective functions, such as the transport of brain-derived neurotrophic factor (BDNF).

Other names

HTT mRNAHD mRNAIT15 mRNAHuntingtin transcriptHuntingtin pre-mRNA