Creyon Bio, Inc, a drug development company focused on transforming nucleic-acid medicine drug discovery to drug engineering, published new research greatly increasing their ability to engineer Oligonucleotide-Based Medicines (OBMs) with minimal off-target effects, which will help us evaluate molecules with a higher standard of precision and live up to the full potential of the “super-modality” of oligonucleotide-based medicines. While Oligonucleotide-Based Medicines (OBMs), like ASOs and siRNAs, have the ability to target precisely the genetic basis of disease by controlling gene expression, there is still a need to understand and minimize off-target effects that would be deleterious. The lack of robust methods that can work genome-wide have presented challenges for the industry. Creyon’s latest research focuses on making OBMs more precise using a method called DoReSeq that can quantify off-target effects across the entire transcriptome with high accuracy, including confidence scores. The paper, titled “A Dose-Response Model for Accurate Detection and Quantification of Transcriptome-Wide Gene Knockdown for Oligonucleotide-Based Medicines”, is available in BioRxiv.
This research allows us to extend beyond current approaches that limit the scope and sensitivity in which we can understand potential off-target liabilities, helping ensure we are making best-in-class OBMs and ultimately moving beyond using slow and failure prone trial-and-error processes for optimizing for safety and activity.
David Pekker, Ph.D., Director of Theory at Creyon Bio, is lead author of the paper. Additional authors are Steven Kuntz, Ph.D., Sr Director of Bioengineering and In Vitro Pharmacology, Monica McArthur, Ph.D., Chief Technology Officer, Tim Nicholson-Shaw, Ph.D., Senior Scientist, Sara Yanke, Research Associate, and Swagatam Mukhopadhyay, Ph.D, Co-founder and Chief Scientific Officer.