2017
DOI: 10.1038/s41467-017-00569-6
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Engineered proteins with sensing and activating modules for automated reprogramming of cellular functions

Abstract: Protein-based biosensors or activators have been engineered to visualize molecular signals or manipulate cellular functions. Here we integrate these two functionalities into one protein molecule, an integrated sensing and activating protein (iSNAP). A prototype that can detect tyrosine phosphorylation and immediately activate auto-inhibited Shp2 phosphatase, Shp2-iSNAP, is designed through modular assembly. When Shp2-iSNAP is fused to the SIRPα receptor which typically transduces anti-phagocytic signals from t… Show more

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Cited by 33 publications
(29 citation statements)
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“…The iSNAPS protein is inserted into macrophages in the study, and it reconnects macrophages, covering the escape signals recognized by the tumor cells and interpreting them as phagocytic signals. In addition, its rapid response and strong lethality can significantly enhance the ability of macrophages to divide, phagocytose, and kill tumor cells rapidly (84).…”
Section: Isnaps Smart Protein Moleculesmentioning
confidence: 99%
See 1 more Smart Citation
“…The iSNAPS protein is inserted into macrophages in the study, and it reconnects macrophages, covering the escape signals recognized by the tumor cells and interpreting them as phagocytic signals. In addition, its rapid response and strong lethality can significantly enhance the ability of macrophages to divide, phagocytose, and kill tumor cells rapidly (84).…”
Section: Isnaps Smart Protein Moleculesmentioning
confidence: 99%
“…The design principle of this intelligent protein molecule can also be used to redesign other immune cells for cancer treatment. At present, the team plans to test iSNAPS in mice and may study its application in other areas (84). This protein may influence not only tumor treatment but also other diseases and self-regulation, and further research is needed.…”
Section: Isnaps Smart Protein Moleculesmentioning
confidence: 99%
“…Utilizing this imaging and analysis protocols, our group has published an array of papers engineering FRET biosensors and quantifying the time courses of dynamic molecular activities for kinases, proteases, and membrane channels in live cells [6,23,24,26,28,40,53,54,56]. Currently, we do not correct for multi-channel cross-talks and bleed-through between fluorophores or estimate pixelwise FRET efficiency by default [57].…”
Section: Discussionmentioning
confidence: 99%
“…Moving forward, the team is planning to test the iSNAPs in mice to see how they could perform in vivo. The researchers are also interested in studying whether the iSNAPs can be harnessed to enhance other native cellular functions to correct various disease pathologies [7].…”
Section: Gerontol and Geriatric Stud Gerontology And Geriatrics Studiesmentioning
confidence: 99%