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

doi:10.1126/science.aba6527

GSTDTAP > 气候变化

DOI	10.1126/science.aba6527
	Designed protein logic to target cells with precise combinations of surface antigens
	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-Rubio; JayLee Johnson; Garreck Lenz; Alisha Nguyen; Suzie Pun; Colin E. Correnti; Stanley R. Riddell; David Baker
	2020-09-25
发表期刊	Science
出版年	2020
英文摘要	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][1] 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 using specific combinations of proteins present on their surfaces. 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. [1]: /lookup/doi/10.1126/science.aba6527
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/296526
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Marc J. Lajoie,Scott E. Boyken,Alexander I. Salter,et al. Designed protein logic to target cells with precise combinations of surface antigens[J]. Science,2020.
APA	Marc J. Lajoie.,Scott E. Boyken.,Alexander I. Salter.,Jilliane Bruffey.,Anusha Rajan.,...&David Baker.(2020).Designed protein logic to target cells with precise combinations of surface antigens.Science.
MLA	Marc J. Lajoie,et al."Designed protein logic to target cells with precise combinations of surface antigens".Science (2020).