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Using a recently developed AAV capsid for efficient in vitro transduction we report the engineering of microglia with CARs (CAR-Mic) targeting phagocytosis of amyloid beta 1\u201242 (A\u03b242). Functional screening of seven CAR constructs in human iPSC-derived microglia revealed up to 6-fold increases in internalized A\u03b2 relative to viral control. CAR-driven phagocytic enhancement was selective for A\u03b2, dependent on intracellular domain signaling, and was confirmed in primary mouse microglia. 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R.R., E.H., H.Z. and A.B. are shareholders in CERimmune Therapeutics. H.Z. has served on scientific advisory boards and\/or as consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}