Preclinical safety assessment of pathogen reduced red blood cells treated with amustaline and glutathione.

ABSTRACT: BACKGROUND:The nucleic acid targeted pathogen reduction (PR) system utilizing amustaline (S-303) and glutathione (GSH) is designed to inactivate blood-borne pathogens and leukocytes in red blood cell concentrates (PR-RBCC). Inactivation is attained after amustaline intercalates and forms covalent nucleic acid adducts preventing replication, transcription, and translation. After pathogen inactivation, amustaline spontaneously hydrolyzes to S-300, the primary negatively charged reaction product; amustaline is below quantifiable levels in PR-RBCC. GSH quenches free unreacted amustaline. STUDY DESIGN AND METHODS:The genotoxic and carcinogenic potential of PR-RBCC, the reaction by-products, and S-300 were assessed in accordance with the International Conference on Harmonization (ICH) guidelines

SUBMITTER: North AK 

PROVIDER: S-EPMC7027779 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature