siRNA was officially designated drug status in 2018 when the FDA approved Alnylam’s patisiran for the treatment of hereditary transthyretin-mediated amyloidosis, followed by multiple other approvals over the last four years. To date, limited biotransformation, reaction phenotyping and structure-activity relationship (SAR) data has been published for siRNA, making it challenging to ascertain which processes are driving ADME and pharmacokinetic/pharmacodynamic (PK/PD) relationship for this modality. The current state of the field will be summarized. Importantly, as the field of siRNA therapeutics is moving beyond GalNAc-conjugated siRNA it will be crucial to understand “the rules” to establish an effective PK/PD relationship. The presentation will discuss how to apply fundamental understanding of ADME properties should be applied to conjugates directed towards tissues beyond the liver as well as describe different type of modlaities used for directed delivery.

Ultilizing the ADME learnings for GalNAc-conjugated siRNA to optimize delivery to tissues outside of the liver

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.