Abstract
Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immune receptor repertoires and the landscape of potential antigens. To address this, we present RAPTR (Receptor-Antigen Pairing by Targeted Retroviruses). RAPTR combines viral pseudotyping and molecular engineering approaches to enable one-pot library on library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cells allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable, and compatible with any cell type, making it easily implemented. These techniques provide a suite of new tools for targeted viral entry, molecular engineering, and interaction screens with broad potential applications.
Competing Interest Statement
The lentiviral targeting approach in this manuscript is the subject of US patent applications with M.E.B., S.G., and C.S.D. as co-inventors. M.E.B. is a founder, consultant, and equity holder of Viralogic Therapeutics and Abata Therapeutics. SKD received unrelated research funding from Novartis Pharmaceuticals, Eli Lilly and Company, and Bristol-Myers Squibb and is a founder, science advisory board member and equity holder in Kojin. MD is a science advisory board member for Neoleukin.