Delivery of nucleic acid therapeutics for cancer immunotherapy

Cancer immunotherapy has shown great potential as witnessed by an increasing number of immuno-oncology drug approvals in the past few years. Meanwhile, the field of nucleic acid therapeutics has made significant advancement. Nucleic acid therapeutics, such as plasmids, antisense oligonucleotides (ASO), small interfering RNA (siRNA) and microRNA, messenger RNA (mRNA), immunomodulatory DNA/RNA, and gene-editing guide RNA (gRNA) are attractive due to their versatile abilities to alter the expression of target endogenous genes or even synthetic genes, and modulate the immune responses. These abilities can play vital roles in the development of novel immunotherapy strategies. However, limited by the intrinsic physicochemical properties such as negative charges, hydrophilicity, as well as susceptibility to enzymatic degradation, the delivery of nucleic acid therapeutics faces multiple challenges. It is therefore pivotal to develop drug delivery systems that can carry, protect, and specifically deliver and release nucleic acid therapeutics to target tissues and cells. In this review, we attempted to summarize recent advances in nucleic acid therapeutics and the delivery systems for these therapeutics in cancer immunotherapy.