Cas9 antigenicity — addressing activation of adaptive host immune response 9255

Abstract Description Virpi Stigzelius 1,2,3; Jacopo Chiaro 2,3; Manlio Fusciello 2,3; Federica D’Alessio 2,3; Salvatore Russo 2,3; Rakesh Chandode 4; Anna Lina Cavallo 5; Vincenzo Cerullo 2,3 & Roberto Nitsch 1 1 Gene Therapy Safety, Clinical Pharmacology and Safety Sciences, AstraZeneca R&D, Sweden; 2 ImmunoViroTherapy Lab, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Finland; 3 Translational Immunology Program, Faculty of Medicine, University of Helsinki, Finland; 4 Clinical Pharmacology and Safety Sciences, AstraZeneca R&D, Sweden; 5 Discovery Cell and Gene Therapy Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, AstraZeneca R&D, Sweden Genome editing tools, such as RNA-guided DNA endonucleases, offer transformative therapeutic potential but raise concerns regarding immunogenicity due to their bacterial origin. To address Cas9 antigenicity we combined epitope modelling and functional level host response stimulation and observed a Cas9-specific T-cell response activation. In therapeutic context, priming and activation of adaptive host responses against the core component of therapeutic modality may results in rejection of the targeted cells and potentially compromising the treatment outcome. Hence, understanding Cas9-antigenicity and ways to mitigate it is crucial for versatile utility of therapeutic genome editing. Funding Sources Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Executive Agency. Neither the European Union nor the European Research Executive Agency can be held responsible for them. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)