Journal
SCIENCE
Volume 370, Issue 6520, Pages 1099-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abc6270
Keywords
-
Categories
Funding
- Genentech Pre-Doctoral Fellowship
- Jane Coffin Childs Memorial Fund Post-Doctoral Fellowship
- NIH [R35 CA197633, P50GM081879, R01 CA196277]
- Howard Hughes Medical Institute
Ask authors/readers for more resources
Living cells often identify their correct partner or target cells by integrating information from multiple receptors, achieving levels of recognition that are difficult to obtain with individual molecular interactions. In this study, we engineered a diverse library of multireceptor cell-cell recognition circuits by using synthetic Notch receptors to transcriptionally interconnect multiple molecular recognition events. These synthetic circuits allow engineered T cells to integrate extra- and intracellular antigen recognition, are robust to heterogeneity, and achieve precise recognition by integrating up to three different antigens with positive or negative logic. A three-antigen AND gate composed of three sequentially linked receptors shows selectivity in vivo, clearing three-antigen tumors while ignoring related two -antigen tumors. Daisy-chaining multiple molecular recognition events together in synthetic circuits provides a powerful way to engineer cellular-level recognition.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available