DIA/FDA Oligonucleotide-Based Therapeutics Conference

Session Chair(s)

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)