RESUMEN
Stimulator of interferon genes(STING)is a key protein in cGAS-STING signaling pathway and plays an important role in immune response mediated by the exogenous or endogenous DNA.This review describes the biological function of STING, the process of cGAS-STING pathway, the classification and administration of STING agonists, and summarizes the currently reported drug delivery systems.The delivery of STING agonists through appropriate drug carriers can overcome the lack of difficult entry, easy enzymatic hydrolysis, short half-life and poor targeting, improve the body's innate and adaptive immunity, and enhance the therapeutic effect of drugs.In conclusion, this paper mainly reviews the research progress of drug delivery system for STING agonists to provide basis for the development of drug delivery system and promote the clinical transformation and application of STING agonists.
RESUMEN
As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes (STING) is triggered by cytosolic DNA from pathogen and host origins, and plays an important role in inducing the secretion of type I interferons and proinflammatory cytokines, thereby defending against viral and intracellular bacterial infections and regulating the production of spontaneous antitumor immune responses in vivo. Thus, STING agonists have shown useful therapeutic effects for pathogen infection and cancer. In the past decade research on STING and its agonists has progressed rapidly. Here, we summarize recent advances in the structure and activation of STING and the mechanism of the cGAS-STING pathway. In particular, we review research advances of STING agonists, analyze the crystal structure of STING in complex with its agonists and the structure-activity relationship of STING agonists, and summarize the strong challenges of developing STING agonists.
RESUMEN
Tumor immunotherapy is a critical field in the development of anticancer drugs. The research of stimulator of interferon genes (STING) agonist provides a new idea for immunotherapy. Innate immune response can effectively be induced by nucleic acids in mammalian cytoplasm. In recent years, a large number of studies have confirmed that the cGAS-cGAMP-STING signaling pathway plays a key role in cytoplasmic DNA recognition and immune defense activation. The dysfunction of cGAS-cGAMP-STING is closely related to the tumorigenesis, and is a potent target for drug development. In this study, based on THP-1 dual cells which are stably expressing cGAS-STING pathway and THP-1 KO-STING cells which are stably depleted STING, a screening method for STING agonists was established by detection of luciferase. Furthermore, the accuracy and sensitivity of the model were verified using positive compound, providing a simple, efficient and accurate screening platform for high-throughput screening of STING agonists.
RESUMEN
Stimulator of interferon genes(STING) are important adaptor proteins in innate immune-related signal pathway. The upstream protein,cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS), is cytosolic DNA sensor. Detection of cytosolic DNA, cGAS-STING pathway can be activated and subsequently activate the type I interferon(IFN) antiviral response. Recent studies indicated that retroviruses especially HIV can activate the host innate immune system through cGAS-STING pathway and trigger robust immune response. In this review, we briefly describe the mechanism of innate immune activated by the newly discovered cGAS-STING pathway and highlight recent progress in STING agonist.
RESUMEN
Stimulator of interferon genes(STING)are important adaptor proteins in innate immune-related signal pathway. The upstream protein,cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS),is cytosolic DNA sensor. Detection of cytosolic DNA,cGAS-STING pathway can be activated and subsequently activate the type Ⅰ interferon (IFN)antiviral response. Recent studies indicated that retroviruses especially HIV can activate the host innate immune system through cGAS-STING pathway and trigger robust immune response. In this review,we briefly describe the mechanism of innate immune activated by the newly discovered cGAS-STING pathway and highlight recent progress in STING agonist.