How to test for immune activation by your therapeutic oligonucleotide
Presenter: Arthur M. Krieg, MD, Checkmate Pharmaceuticals
Date: 19 April 2018
Description: RNA and DNA oligonucleotides with charged backbones commonly cause immune activation, which can be recognized by appropriate in vitro and/or in vivo testing.
Eukaryotic innate immune systems have evolved multiple receptors to detect foreign or self nucleic acids as signs of infection or tissue damage. Receptors to detect both RNA and DNA are present in both the endosomes and cytoplasm of many cells, and are commonly activated by therapeutic oligonucleotides. Recognition of these effects is critical to appropriate interpretation of experimental data. Various strategies involving sequence selection and nucleotide/backbone modification can be used to reduce undesired immune stimulatory effects.
In this webinar Art will share his expertise in how to best detect innate immune system activation and distinguish between effect of such activation and your therapeutic oligonucleotide. The presentation will be followed by a Q&A session where you can ask Art your questions during the broadcast.
For some background watch Arts’ presentation on designing and using immune stimulatory oligonucleotides:
Arthur M. Krieg, MD has worked in the oligonucleotide field since the 1980s. Most recently he founded Checkmate Pharmaceuticals to develop novel oligonucleotides for cancer immunotherapy. Prior to that role Art was CSO at Sarepta until July 2014; co-founder and CEO at RaNA Therapeutics from 2011 to 2013; CSO of Pfizer’s Oligonucleotide Therapeutics Unit from 2008 to 2011; and co-founder, CSO of Coley Pharmaceutical Group from 1997 until its acquisition and incorporation into Pfizer in 2008. Art discovered the immune stimulatory CpG DNA motif in 1994, which led to a new approach to immunotherapy and vaccine adjuvants. Based on this technology he co-founded Coley Pharmaceutical Group in 1997, discovering and taking 4 novel oligonucleotides into clinical development. Art co-founded the first antisense journal, Nucleic Acid Therapeutics, which he edited for 16 years, and the Oligonucleotide Therapeutics Society, for which he is currently serving as President for the 2017-2018 term. He is a Professor in the University of Massachusetts RNA Therapeutics Institute and he serves on the scientific advisory boards of several companies developing oligonucleotide therapeutics.
Art graduated from Haverford College in 1979, received his MD from Washington University in 1983, and completed a residency in Internal Medicine at the University of Minnesota in 1986. He was a Staff Fellow at the NIH in the Arthritis Institute from 1986 to 1991, when he joined the University of Iowa, becoming Professor of Internal Medicine in the Division of Rheumatology. He has had 19 years of patient care experience, although his focus has always been on basic research and teaching. Art left academia and joined Coley full-time in 2001. He has published more than 250 scientific papers and is an inventor on 48 issued US patents covering oligonucleotide technologies.