WT1 antisense oligonucleotides

WT1 antisense oligonucleotides are a class of investigational nucleic acid-based therapeutics designed to selectively downregulate the expression of the Wilms' Tumor 1 (WT1) protein. WT1 is a zinc-finger transcription factor that plays a critical role in cell proliferation, differentiation, and apoptosis; while essential for normal urogenital development, its overexpression is a hallmark of various malignancies, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and solid tumors like breast cancer. These antisense oligonucleotides (ASOs), such as the 2'-O-methoxyethyl (MOE) modified chimeric compounds ISIS 16609 and ISIS 16601 developed by Ionis Pharmaceuticals, work by binding to specific sequences of WT1 mRNA through Watson-Crick base pairing. This binding typically induces RNase H-mediated cleavage of the target mRNA or physically blocks translation, leading to reduced WT1 protein levels and subsequent inhibition of tumor cell growth and induction of apoptosis. Although extensively studied in preclinical models and early-phase clinical trials, no specific WT1 ASO has yet reached regulatory approval.

Other names

WT1 ASOWT-1 ASOWT 1 ASOWT1 antisense oligodeoxynucleotidesWT-1 antisense oligodeoxynucleotidesWT 1 antisense oligodeoxynucleotidesWilms' tumor 1 antisense oligonucleotides