Stereopure oligo therapy for ALS

Abstract

The first antisense oligonucleotide (ASO) approved for clinical use targeted cytomegalovirus (CMV) and was designed to treat CMV retinitis. Although this patient market is limited, it nevertheless triggered increased interest in the technology. Despite their versatility, phosphorothioate ASOs possess chirality at each nucleotide, resulting in less stable hybrids with their RNA complement. Thus, a 20-mer exists as hundreds of thousands of chiral forms that differ in activity, including the ability to hybridize to their target.