To scramble or not: steric blocking 2′-MOE/PS control antisense oligonucleotides across cellular models

Currently, fourteen ASOs have been FDA/EMA-approved, with many more in preclinical development. An important requirement for preclinical studies is the inclusion of negative controls to properly assess the efficacy of candidate ASOs.

As commonly used scrambled or sense ASOs may elicit unwanted off-target effects that could influence downstream data analysis, there is a high need for the inclusion of additional negative control ASOs that are well-characterized and well-tolerated. In this study, we designed and evaluated generic control ASOs (cASOs) across seven different cellular models. Characterization at the RNA and protein level revealed potential ASO toxicity mechanisms as well as species-specific and cell-type specific effects.