Nanoparticles for nucleic acid delivery: Applications in cancer immunotherapy

Immunotherapy has recently emerged as a powerful tool for cancer treatment. Early clinical successes from cancer immunotherapy have led to a growing list of FDA approvals, and many new therapies are in clinical and preclinical development. Nucleic acid therapeutics, including DNA, mRNA, and genome editing systems, hold significant potential as a form of immunotherapy due to its robust use in cancer vaccination, adoptive T-cell therapy, and gene regulation. However, these therapeutics must overcome numerous delivery obstacles to be successful, including rapid in vivo degradation, poor uptake into target cells, required nuclear entry, and potential in vivo toxicity in healthy cells and tissues. Nanoparticle delivery systems have been engineered to overcome several of these barriers as a means to safely and effectively deliver nucleic acid therapeutics to immune cells. In this Review, we discuss the applications of nucleic acid therapeutics in cancer immunotherapy, and we detail how nanoparticle platforms have been designed to deliver mRNA, DNA, and genome editing systems to enhance the potency and safety of these therapeutics.