Not long ago, I wrote about an important paper that we published (Shen et. al, NBT, 2019) which, for the first time, provides a step-by-step molecular mechanism explaining most of the toxicities of ASOs and a straightforward medicinal chemical solution that dramatically enhances the therapeutic index of toxic ASOs. As you might imagine, we will be publishing a number of papers that provide more detail and expand our observations. Two papers, Vickers et.al. and Migawa et.al are now published in Nucleic Acids Research, or NAR (2019). The Vickers et. al paper provides more detail on the binding of safe and toxic ASOs to two key proteins, P54 and RNAse H1, as well as more information about the composition of the toxic protein/RNA ASO complex. The Migawa et.al. paper expands the SAR of modifications that may reduce negative effects of some ASOs. I think that you may find these papers of interest and they will set you up to understand a large number of papers that are in preparation.
Ionis papers provide insight into the characteristics of antisense medicines
