The Limits of Imperfect: What Do We Know About Low-Homology siRNA Off-Targets?
Time: 9:00 am
day: Conference Day Two
Details:
- siRNA therapeutics are rigorously designed and screened to minimize off-target effects; this is done initially in silico by sequence alignment-based approaches, traditionally using relatively high homology thresholds
- Surprisingly, performing unbiased RNAseq experiments reveals that a significant number of DEGs with low-homology alignments may also be regulated. Here we present a global analysis of what these alignments look like and how they may be informed by our understanding of RNAi biology
- This global analysis was validated by a series of experiments designed to probe the limits of these “imperfect” alignments. Taken together, these findings can help inform future in-silico off-target predictions while minimizing the number of false positives
