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 Although the relative contribution of mRNA/pregenomic RNA degradation and immune stimulation is still under investigation, we would like to make the following comments.