Mutant huntingtin messenger RNA (mHTT mRNA) containing single nucleotide polymorphism rs7685686 (mHTT mRNA (rs7685686))

The target is the mutant huntingtin (HTT) messenger RNA (mRNA) transcript that specifically contains the single nucleotide polymorphism (SNP) rs7685686. This SNP is frequently found in linkage disequilibrium with the pathogenic CAG repeat expansion in the HTT gene, making it a viable target for allele-specific silencing in Huntington's disease (HD) patients (Southwell et al., 2014, Nature Communications). HD is a neurodegenerative disorder characterized by the production of toxic mutant huntingtin protein (mHTT), which leads to neuronal death, particularly in the striatum (Ross & Tabrizi, 2011, Lancet Neurology). By targeting the mRNA sequence containing rs7685686, therapeutic agents such as antisense oligonucleotides (ASOs) can selectively induce the degradation of the mutant transcript while sparing the wild-type HTT mRNA (Skotte et al., 2014, PLOS ONE). This approach is designed to maintain the essential biological functions of the wild-type protein, which is involved in axonal transport and neuroprotection (Zuccato et al., 2010, Physiological Reviews). Clinical development of such allele-specific therapies requires patient stratification based on the presence of the rs7685686 SNP to ensure target engagement (Kay et al., 2014, BMC Medical Genetics). The use of rs7685686 as a molecular handle allows for the treatment of a significant subpopulation of HD patients who carry this specific genetic signature.

Other names

Mutant HTT mRNAmHTT mRNA (rs7685686)Huntingtin mRNA containing rs7685686SNP1-containing huntingtin transcript

Allele-specific knockdown of mutant huntingtin mRNA via RNase H-mediated degradation or RNA interference-mediated cleavage