Ling-Zu Kong1,2, Seok-Min Kim1, Chunli Wang1, Soo Yun Lee1, Se-Chan Oh1, Sunyoung Lee1,3, Seona Jo1,4 and Tae-Don Kim1,4,5,6
1Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
2Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Republic of Korea.
3Department of Life Sciences, Korea University, Seoul 02841, Korea.
4Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea.
5Biomedical Mathematics Group, Institute for Basic Science (IBS), Daejeon, Republic of Korea.
6Department of Biopharmaceutical Convergence, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Corresponding author : Correspondence to Tae-Don Kim.
Nucleic acid sensing is involved in viral infections, immune response-related diseases, and therapeutics. Based on the composition of nucleic acids, nucleic acid sensors are defined as DNA or RNA sensors. Pathogen-associated nucleic acids are recognized by membrane-bound and intracellular receptors, known as pattern recognition receptors (PRRs), which induce innate immune-mediated antiviral responses. PRR activation is tightly regulated to eliminate infections and prevent abnormal or excessive immune responses. Nucleic acid sensing is an essential mechanism in tumor immunotherapy and gene therapies that target cancer and infectious diseases through genetically engineered immune cells or therapeutic nucleic acids. Nucleic acid sensing supports immune cells in priming desirable immune responses during tumor treatment. Recent studies have shown that nucleic acid sensing affects the efficiency of gene therapy by inhibiting translation. Suppression of innate immunity induced by nucleic acid sensing through small-molecule inhibitors, virus-derived proteins, and chemical modifications offers a potential therapeutic strategy. Herein, we review the mechanisms and regulation of nucleic acid sensing, specifically covering recent advances. Furthermore, we summarize and discuss recent research progress regarding the different effects of nucleic acid sensing on therapeutic efficacy. This study provides insights for the application of nucleic acid sensing in therapy.