Reply to: "Bepirovirsen/GSK3389404: Antisense or TLR9 agonists?"

Dr Andrew Vaillant has hypothesized that the principal mechanism of action of GSK3389404 (N-acetylgalactosamine [GalNAc]-conjugated antisense oligonucleotide [ASO]) and bepirovirsen (non-GalNAc-conjugated ASO with the same target sequence as GSK3389404) is through immune stimulation rather than mRNA degradation. [1] Vaillant A. Bepirovirsen/GSK3389404: antisense or TLR9 agonists?. J Hepatol. 2022; https://doi.org/10.1016/j.jhep.2022.09.002 Abstract Full Text Full Text PDF PubMed Google Scholar Although the relative contribution for hepatitis B virus (HBV) mRNA/pregenomic RNA degradation and immune stimulation is still under investigation, we would like to make the following comments. Bepirovirsen / GSK3389404: antisense or TLR9 agonists?Journal of HepatologyPreviewnot applicable. Full-Text PDF Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapyJournal of HepatologyVol. 77Issue 4PreviewBepirovirsen, an antisense oligonucleotide targeting pregenomic and mRNA transcripts of HBV, has been conjugated to N-acetyl galactosamine (GSK3389404) to enhance hepatocyte delivery. This dose-finding study was the first to assess GSK3389404 for chronic HBV infection. Full-Text PDF Open Access