title: Potential therapeutic targets in the process of nucleic acid recognition: opportunities and challenges.
abstract: Nucleic acid recognition or sensing (NAS) is accepted as a fundamental function in the host defense against self or foreign genetic elements. Abnormal recognition or interpretation of microbial-origin pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) can lead to infections or autoimmune diseases (ADs). Modulation of the NAS process represents a path toward the development of novel vaccines or drugs, through targets such as myeloid differentiation primary-response protein 88 (MyD88) and tumor necrosis factor (TNF) receptor-associated factor (TRAF) 3 and 6 in Toll-like receptor (TLR)-mediated signaling pathways. DNA helicases can be targeted by arresting replication and the breakage of DNA double strands. Stimulator of interferon (IFN) genes (STING) may act as a therapeutic target by upregulation of the STING-dependent pathway or vaccination with cyclic GMP-AMP (cGAMP) synthase (cGAS)-catalyzed reaction products. Several challenges are faced before and during clinical therapy. NAS can be an important breakthrough for molecular targets and therapies. The specificity of drug delivery, potential of long-term genotoxicity, risk of tumorigenesis, duration of drug efficacy, and drug metabolism should be further validated.
authors.affiliation: Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China. Electronic address: shoahenghe@hotmail.com.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: He
authors.affiliation: Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China; Institute of Frontier Medicine, Shirokanekai Medical Association, Tokyo, Japan.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Mao
authors.affiliation: Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Sun
authors.affiliation: Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China; Institute of Frontier Medicine, Shirokanekai Medical Association, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Allergy and Clinical Immunology Research Centre, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Minhang Hospital, Zhongshan Hospital, Fudan University, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai, China. Electronic address: xiangdong.wang@clintransmed.org.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D004265:DNA Helicases / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D009696:Nucleic Acids / Q000276:immunology* / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000276:immunology / Q000378:metabolism; D020365:RNA Helicases / Q000276:immunology / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D004265:DNA Helicases; D008565:Membrane Proteins; D009696:Nucleic Acids; D009713:Nucleotidyltransferases; D020365:RNA Helicases; D051192:Receptors, Pattern Recognition; C532857:STING1 protein, human; D000099197:STING Protein; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: DAMPs; DNA and RNA sensing; PAMPs; Toll-like receptor; innate immunity; pattern recognition receptor