Genome Editing Using mRNA-Lipid Nanoparticles For CAR T Cell Therapy

The advancement of genome editing technologies has empowered scientists to precisely target and modify the genomic sequences within a living organism. This capability has expanded our comprehension of the genetic foundations of human disease, facilitating the creation of more accurate cellular and animal models. Despite these strides, delivering gene editing tools to target cells has presented a significant challenge. The development of new technologies for safe and efficient gene delivery, capable of overcoming payload limitations, holds the key to unlocking the full potential of gene editing strategies. This, in turn, opens up avenues for exploring novel approaches to cancer treatment and beyond.

Gene engineering of T cells to produce new cancer immunotherapies, such as chimeric antigen receptor (CAR)-T cell therapy, has revolutionized cancer treatment. While current autologous CAR-T immunotherapies have exhibited high clinical success, there is a pressing need to enhance safety and efficacy profiles. Next-generation CAR-T designs focus on elevating CAR-T cell potency, mitigating off-target effects, expanding therapeutic targets beyond liquid cancers, and manufacturing universal CAR-T cells sourced from allogeneic donors. These new strategies necessitate more complex CRISPR/Cas9-enabled genetic engineering approaches, wherein the chosen gene delivery method plays a central role in determining gene editing efficiency, safety, and scalability.