anti-HDV antisense oligonucleotides

Anti-HDV antisense oligonucleotides (ASOs) represent an investigational therapeutic platform designed to target and destroy the hepatitis delta virus (HDV) genome. Developed primarily by Aligos Therapeutics, these direct-acting antivirals (DAAs) are synthetic 5-10-5 gapmer ASOs that target conserved regions of HDV RNA. Unlike small interfering RNAs (siRNAs) which primarily act in the cytoplasm, ASOs can function in both the cytoplasm and the nucleus, making them uniquely suited to inhibit the nuclear rolling-circle replication process of HDV. Preclinical studies of lead candidates, such as ALG-215007, have demonstrated potent, single-digit nanomolar inhibition of HDV replication markers (including HDAg and HDV RNA) and impairment of viral propagation in vitro. Additionally, these ASOs may act as host-targeting agents (HTAs) by stimulating innate immune responses, such as Toll-like receptor 8 (TLR8) activation, providing a dual-action therapeutic strategy for chronic HDV infection.

Other names

anti-HDV ASOsantisense oligonucleotides targeting HDVHDV-targeted ASOsHDV-targeted antisense oligonucleotides