Mutant huntingtin messenger RNA containing a target single nucleotide polymorphism (mHTT mRNA (SNP-specific))

Mutant huntingtin messenger RNA (mHTT mRNA) containing a target single nucleotide polymorphism (SNP) is a precision therapeutic target for Huntington's disease (HD) (Skotte et al., 2014, PLoS One). HD is caused by a CAG repeat expansion in the HTT gene, resulting in a toxic protein that leads to neurodegeneration (Tabrizi et al., 2022, Lancet Neurology). Because the wild-type huntingtin protein is critical for neuronal health, therapeutic strategies often aim to selectively reduce the mutant form while preserving the wild-type (Datson et al., 2017, Gene Therapy). This is achieved by targeting SNPs that are in linkage disequilibrium with the CAG expansion, allowing antisense oligonucleotides (ASOs) to distinguish between the two alleles (Wave Life Sciences, 2024). Drugs like WVE-003 are designed to bind to these specific SNPs, triggering RNase H-mediated degradation of only the mutant mRNA (Vissuanathan et al., 2024, Journal of Huntington's Disease). This approach minimizes the risk of loss-of-function toxicity associated with total huntingtin knockdown.

Other names

SNP-specific mutant huntingtin mRNAAllele-specific HTT mRNAMutant HTT transcriptmHTT mRNA containing SNP

Allele-specific knockdown via RNase H-mediated degradation of the mutant huntingtin mRNA transcript.