Abstract: A nucleic acid construct for targeting and integrating a CD3 zeta-deficient chimeric antigen receptor (CAR) fragment into an endogenous CD3 zeta/CD247 gene of a host genome. Also disclosed is a genetically modified human cell expressing an exogenous nucleic acid sequence encoding a CD3 zeta deficient CAR fragment, integrated in-frame into the endogenous CD3 zeta/CD247 gene for gene fusion, to form a functional CAR including an exogenous CAR fragment fused with an endogenous CD3 zeta domain.