A transformative immunotherapy approach enables in vivo generation of chimeric antigen receptor (CAR) T cells directly within patients using antibody-conjugated lipid nanoparticles (tLNPs). These tLNPs, engineered with the novel ionizable lipid L829 and decorated with CD5-targeting antibodies, deliver mRNA encoding CAR constructs specifically to T cells, circumventing ex vivo cell engineering complexities. This system enhances targeting efficiency by avoiding hepatic clearance, offering a scalable, safe, and cost-effective alternative strategy that may dramatically accelerate CAR T cell therapeutic availability for cancer and autoimmune diseases.