Work from my group has demonstrated that proteins determine the fate of PS ASOs in all biological systems, identified the key proteins involved in cellular pharmacodynamics, pharmacokinetics and toxicology, characterized the binding of PS ASO to many of the critical proteins and demonstrated that most cytotoxic PS ASOs in all cells and organs studied are to interactions with paraspeckle proteins and RNAse H1 that delocalize … Continue reading PS ASO Induced Aggregates Undergo Phase separations. »

In this paper, we continue our exploration of the molecular mechanisms by which PS ASOs enter and distribute within cells such that they can be pharmacologically active.  We show that M6PR plays a critical role in releasing PS ASOs from late endosomes. We now believe that we have identified most of the endosomal means of productive uptake and intracellular distribution of PS ASOs. We are assessing the … Continue reading Update on Core Antisense Research »