Potential therapeutic targets in the process of nucleic acid recognition: opportunities and challenges

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.