Figure 1.

Schematic depiction of common nucleic acid therapeutics for cancer immunotherapy. Immunostimulatory (IS) nucleic acids of PAMPs are detected by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) on the endosome membrane and cyclic GMP-AMP synthase (cGAS) in the cytosol that culminate in the production of type I interferons (IFNs) and proinflammatory cytokines, leading to the promotion of anticancer immune responses. Moreover, genetic carriers such as plasmids and mRNA can express functional RNA or protein/peptides that promote anticancer immune responses. Gene-regulating nucleic acids, such as siRNA/shRNA, gene activating nucleic acids, antisense oligonucleotides, and gene-editing nucleic acids, can regulate immune-related genes for the activation of anticancer immune responses. Other nucleic acids such as aptamers can function as agonists or antagonists against immune-related molecular targets so as to promote anticancer immune responses. For cancer immunotherapy, these nucleic acid immunotherapeutics can be engineered to function in a wide variety of cells including antigen-presenting cells (APCs), T cells or natural killing (NK) cells, and cancer cells. dsDNA, double-stranded DNA; dsRNA, double-stranded RNA; STING, stimulator of interferon genes; cGAS, cyclic GMP-AMP synthase; TBK1, TANK-binding kinase 1; Stat6, signal transducer and activator of transcription 6; IRF3, interferon regulatory factor 3; IKK, IκB kinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TLR, Toll-like receptors; TRIF, TIR-domain-containing adapter-inducing interferon-β (TRIF); MHC, major histocompatibility complex; GM-CSF, granulocyte-macrophage colony-stimulating factor; CARs, chimeric antigen receptors; CDNs, cyclic dinucleotides; TAA, tumorassociated antigen.