Designed protein logic to target cells with precise combinations of surface antigens

In this study, we design colocalization-dependent protein switches (Co-LOCKR) that perform AND, OR, and NOT Boolean logic operations. These switches activate through a conformational change only when all conditions are met, generating rapid, transcription-independent responses at single-cell resolution within complex cell populations. We implement AND gates to redirect T cell specificity against tumor cells expressing two surface antigens while avoiding off-target recognition of single-antigen cells, and three-input switches that add NOT or OR logic to avoid or include cells expressing a third antigen. Thus, de novo designed proteins can perform computations on the surface of cells, integrating multiple distinct binding interactions into a single output.

Source: ScienceNOW - September 23, 2020 Category: Science Authors: Lajoie, M. J., Boyken, S. E., Salter, A. I., Bruffey, J., Rajan, A., Langan, R. A., Olshefsky, A., Muhunthan, V., Bick, M. J., Gewe, M., Quijano-Rubio, A., Johnson, J., Lenz, G., Nguyen, A., Pun, S., Correnti, C. E., Riddell, S. R., Baker, D. Tags: Biochemistry, Molecular Biology reports Source Type: news