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Publication Abstract from PubMed

Precise cell targeting is challenging because most mammalian cell types lack a single surface marker that distinguishes them from other cells. A solution would be to target cells based on specific combinations of proteins present on their surfaces. 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 3-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.

Designed protein logic to target cells with precise combinations of surface antigens.,Lajoie MJ, Boyken SE, Salter AI, Bruffey J, Rajan A, Langan RA, Olshefsky A, Muhunthan V, Bick MJ, Gewe M, Quijano-Rubio A, Johnson J, Lenz G, Nguyen A, Pun S, Correnti CE, Riddell SR, Baker D Science. 2020 Aug 20. pii: science.aba6527. doi: 10.1126/science.aba6527. PMID:32820060^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.