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Session 4 Track 2: Off-Target Effects
Session Chair(s)
Sebastien Burel, PhD
Executive Director, Ionis pharmaceuticals, United States
James Wild, MS
Pharmacologist, CDER, FDA, United States
The sequence-specific interaction of single- and double-stranded oligonucleotides with a variable range of off-target sites on pre-mRNA, mRNA and miRNA can result in hybridization-dependent toxicity. Similar off-target concerns, and the risk of introducing nuclease-induced off-target mutations exist for guide RNA in CRISPR-Cas genome-editing nucleases. This session will examine in silico and in vitro methods and strategies for identifying, assessing, and de-risking off-target hybridization for oligonucleotides and CRISPR genome editors. In addition, novel off-target assessment of steric-blocking and splice modulating oligonucleotides will be presented and discussed.
Learning Objective : At the conclusion of this session, participants should be able to:
- Recognize and differentiate the scope of mechanisms contributing to off-target effects for oligonucleotides and CRISPR genome editors
- Compare and contrast the application of multiple in silico and in vitro methods for assessing off-target effects
- Formulate strategies for analysis of off-target hybridization for different classes of oligonucleotides
Speaker(s)
Off-target Effects of CRISPR
Shengdar Q. Tsai, PhD
Assistant Member, St. Jude Faculty, Department of Hematology, St. Jude Children's Research Hospital, United States
De-risking of Off-Target Effects
Joanna Harding, MSc
Director, Toxicology Project Lead, CVRM Safety, AstraZeneca, United Kingdom
Off-target Assessment for Splice Modulators
Erle Holgersen
Research Scientist, Deep Genomics, Canada