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Date: May 15, 2025
Time: 11-12pm EDT / 5-6pm CEST
Join us for this Trainee Spotlight webinar featuring trainee Daniel van Leeuwen, poster award winner at the 2024 OTS Annual Meeting.
Title: Deciphering the impact of toxic antisense oligonucleotide (ASO) gapmer off-target (OT) RNA degradation on OT protein level
Presentation Description:
One of the potential safety concerns for antisense oligonucleotide (ASO) gapmers are hybridization dependent off-target (OT) effects. This occurs when ASO gapmers bind unintended (m)RNA transcripts via Watson-Crick hybridization that results in meaningful level of RNase H mediated degradation of the OT transcript. Importantly, despite reduction in protein levels being the main safety concern for OT effects, the OT assessment strategies described today don’t include default assessment on protein level. Here, we performed a pilot experiment in hepG2 cells combining RNA sequencing with fast proteomics analysis at different time points after transfection of ASOs with different number of predicted OTs and in vitro toxicity profiles.
