Tag Archives: medicine

Uncategorized

Insights into innate immune activation via PS-ASO-Protein-TLR9 Interactions

July 15, 2022 : Pollak,A.J., et al, NAR https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkac618/6644951 It has long been known that nucleic acids that have CpG motifs can activate the immune system and that DNA like nucleic acids do that by interacting with TLR9 located in late endosomes. It has also been shown that PS ASOs that do not have CpG motifs can activate the innate immune system in a TLR9 … Continue reading Insights into innate immune activation via PS-ASO-Protein-TLR9 Interactions »

Blogs

PS ASO Induced Aggregates Undergo Phase separations.

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. »

Blogs

Update on Core Antisense Research

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 »

Blogs

NEJM highlights Waylivra™ (volanesorsen)

The results of the Phase three study of WAYLIVRA (volanesorsen) in patients with familial chylomicronemia syndrome (FCS) were recently published in the New England Journal of Medicine (NEJM) (Witzum, et al., 2019). FCS patients have severely elevated triglycerides (often >2000 mg/dl). This drug is now approved in the EU and being considered for approval by the U.S. Food and Drug Administration (FDA). To date, it … Continue reading NEJM highlights Waylivra™ (volanesorsen) »