Dr. Chandrabali Bhattacharya, Ph.D., Assistant Professor, UNLV Department of Chemistry and Biochemistry
"mRNA nanomedicine: the next-generation therapeutics"
Messenger RNA (mRNA) can dictate the cellular machinery to produce any protein and help cure any disease. However, the use of mRNA is restricted by molecular instability and in vivo delivery barriers. Lipid nanoparticles (LNP) have emerged as a promising technology for mRNA delivery without the drawbacks associated with viral delivery. However, the major roadblock in fully unlocking the potential of mRNA drugs is the lack of efficient and selective delivery vehicles, and most of the targets are “undruggable”. One particular application is engineering T cells with Chimeric antigen receptors (CAR). CAR T-cell therapy or ‘living drug’ has shown unprecedented clinical response against refractory and relapsed acute lymphoblastic leukemia cases with complete remission. This is expensive ($500k) and involves modification of the patient's T cells outside the body and reinjection. Moreover, T cells are notoriously difficult to modify and require electroporation or virus-mediated processes, which can result in membrane disruption, loss of cytoplasmic content, and lower yield. Surviving cells may experience cytotoxicity and altered protein expression, leading to side effects in treatment. We are developing special targeted LNPs that can modify T cells in vivo and kill tumors, bypassing the requirement of adoptive cell transfer with a single injection.