MutS homolog 3 (MSH3) mRNA (MSH3 mRNA)

MutS homolog 3 (MSH3) mRNA is the transcript encoding the MSH3 protein, which is a critical component of the MutS beta complex involved in DNA mismatch repair (MMR). While MSH3 typically functions to maintain genomic integrity by repairing insertion-deletion loops, it has been identified as a primary driver of somatic CAG repeat expansion in neurodegenerative disorders such as Huntington's disease [PubMed: 28842173]. In these conditions, MSH3 promotes the progressive lengthening of toxic repeat sequences in neurons, a process that correlates with earlier disease onset and increased severity [PubMed: 31406348]. Therapeutic targeting of MSH3 mRNA, primarily through antisense oligonucleotides (ASOs) like TTX-334 or WVE-MSH3, aims to reduce MSH3 protein expression to stabilize these repeats and delay disease progression. This approach is considered a disease-modifying strategy because it addresses the genetic instability at the root of the pathology. However, because MSH3 is necessary for normal DNA repair, therapeutic knockdown must be carefully managed to avoid inducing secondary mutations or increasing cancer risk [UniProt: P20585]. Current drug development efforts focus on achieving a therapeutic window that reduces repeat expansion without completely abolishing essential repair functions.

Other names

MutS homolog 3 messenger RNAhMSH3 mRNAMismatch repair protein Msh3 mRNAMSH3 transcript

Antisense oligonucleotide-mediated degradation of mRNA to reduce MSH3 protein levels and inhibit somatic CAG repeat expansion.