A novel immunotherapy approach enables direct in vivo creation of CAR T cells using targeted lipid nanoparticles (tLNPs), bypassing complex ex vivo cell engineering processes. This strategy employs lipid nanoparticles functionalized with antibodies targeting the CD5 protein on T cells, delivering mRNA encoding CAR constructs directly into patients' T cells to program them against cancer or autoimmune diseases. The use of a specially designed ionizable lipid (L829) enhances delivery specificity and avoids rapid clearance by the liver. This breakthrough could dramatically simplify CAR T cell therapy manufacturing, reduce costs, and improve accessibility.