Programming immunity in situ: A new frontier of in vivo cell engineering

In vivo cell engineering enables the direct programming of immune cells inside patients. Instead of isolating, modifying, and reinfusing cells, therapeutic instructions are delivered directly to selected immune cells through lipid nanoparticles or viral vectors. This approach could facilitate rapid and scalable deployment of varied immune cell therapies across disease contexts. Early clinical studies in oncology and autoimmunity demonstrate increasing technical and clinical feasibility. The next challenge lies in enhancing precision to ensure that vectors reach the target cell type and tissue, deliver the appropriate payload, and produce desired transient or durable activity. Progress in targeting ligands, vector design, biodistribution control, and genome editing is beginning to address these barriers. Ensuring safety against immunogenicity, inflammatory toxicity, off-target editing, and uncontrolled persistence remains a central priority. By mastering these constraints, in vivo engineering could turn endogenous immune cells into therapeutic agents generated directly in the body, expanding cell therapy to diseases refractory to current modalities.