Huntington’s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the HTT gene resulting in mHTT protein production. While mHTT protein is causative for disease, preclinical studies suggest loss of wild-type HTT (wtHTT) may contribute to neuronal damage. Therefore, the ability to selectively lower production of mHTT protein while maintaining wtHTT protein levels holds great promise for HD treatment.

Standard chemical modifications to improve stability and cellular uptake of ASOs include incorporation of a phosphorothioate (PS) backbone linkage and modification of the nucleotide sugar at the 2’ position. PS substitution converts each achiral phosphodiester (PO) linkage into a chiral PS center using one of two stereochemical configurations (Sp or Rp). Through Wave’s proprietary technology, we can control the three-dimensional structure of nucleic acid compounds to produce a more consistent molecular entity.