Huntingtin mRNA (Htt1a transcript) (Htt1a mRNA)

The Htt1a transcript is a truncated messenger RNA (mRNA) isoform of the Huntingtin (HTT) gene, generated by the aberrant retention of intron 1 during splicing. This transcript is a critical therapeutic target in Huntington's disease (HD) because it is translated into a highly toxic exon 1 HTT protein fragment that serves as a primary seed for pathogenic protein aggregation. siRNA-634 and siRNA-486 are experimental small interfering RNAs designed to selectively bind and degrade the Htt1a mRNA through the RNA interference (RNAi) pathway. By specifically targeting this truncated transcript, these siRNAs aim to reduce the burden of toxic protein species while potentially sparing the expression of the essential full-length HTT protein. Recent studies in knock-in mouse models suggest that silencing Htt1a is more effective at preventing hippocampal neurodegeneration and transcriptional dysfunction than targeting the full-length HTT mRNA alone.

Other names

HTT exon 1 transcriptIntron 1-retained HTT transcriptTruncated Huntingtin mRNAHtt1aHTT1a

RNA interference (RNAi) mediated degradation of the Htt1a transcript to inhibit the production of toxic exon 1 Huntingtin protein.