Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles

CRISPR-based genome editing has rapidly advanced immune cell engineering, creating opportunities to enhance functionality, persistence, and specificity in cancer, infectious, and autoimmune diseases. The translation of these strategies depends critically on safe and efficient delivery systems. Viral vectors achieve high efficiency, but face limitations related to immunogenicity, genomic integration, and manufacturing scalability. Non-viral methods such as electroporation are effective for ex vivo editing yet remain unsuitable for in vivo use. Lipid nanoparticles (LNPs) have emerged as a clinically validated, scalable, and biocompatible alternative capable of delivering CRISPR cargo in the form of DNA, mRNA, or ribonucleoproteins. Recent innovations, including selective organ targeting, ligand conjugation, and sequence-level translational control are expanding their precision and versatility in immune cell engineering. Despite these advances, major challenges remain, including suboptimal endosomal escape, extrahepatic targeting, and immune trade-offs such as the PEG dilemma. By critically synthesizing current progress and limitations, this review highlights the central role of LNPs in enabling CRISPR-based immune engineering and outlines future directions for clinical translation.