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

• DOI: 10.1126/science.aba6527
• Publication Date: 2020-08-20T23:14:00Z
• Authors: Marc J. Lajoie; Scott E. Boyken; Alexander I. Salter; Jilliane Bruffey; Anusha Rajan; Robert A. Langan; Audrey Olshefsky; Vishaka Muhunthan; Matthew J. Bick; Mesfin Gewe; Alfredo Quijano-R...; JayLee Johnson; Garreck Lenz; Alisha Nguyen; Suzie Pun; Colin E. Correnti; Stanley R. Riddell; David Baker
• Keywords: Computers, Molecular; Protein Conformation; Antigens, Surface; Cell Membrane; Proteins; Protein Engineering; 3. Good health

Logic at the cell surface

A major challenge in medical interventions is to target only diseased cells. Although there are biomarkers characteristic of certain cancers, for example, it is unlikely that a single marker can specify a particular cell type. Lajoie et al. addressed this problem by designing protein switches called Co-LOCKR that bind to antigens on the cell surface and activate through a conformational change only when there is a precise combination of antigens. They designed switches that can perform AND, OR, and NOT logic. On the path toward applying this technology, they used Co-LOCKR to direct chimeric antigen receptor T cells to tumor cells expressing specific antigens.

Science , this issue p. 1637