Conjugated STING agonists

An innate immune system is the first line of defense and prevents the host from infection and attacks the invading pathogens. Stimulator of interferon genes (STING) plays a vital role in the innate immune system. STING activation by STING agonists leads to phosphorylation of TANK-binding kinase 1 (T...

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Bibliographic Details
Main Authors: Shuhao Qu, Hong Dai
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Therapy: Nucleic Acids
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Online Access:http://www.sciencedirect.com/science/article/pii/S2162253125000848
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Summary:An innate immune system is the first line of defense and prevents the host from infection and attacks the invading pathogens. Stimulator of interferon genes (STING) plays a vital role in the innate immune system. STING activation by STING agonists leads to phosphorylation of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) with the release of type I interferons and proinflammatory cytokines, further promoting the adaptive immune response and activating T cells by increased antigen presentation. Natural STING agonist cyclic dinucleotides (CDNs) encounter many defects such as high polarity by negative charges, low stability and circulative half-life, off-target systemic toxicity, and low response efficacy in clinical trials. To overcome these challenges, massive efforts have addressed chemical modifications of CDNs, development of non-CDN STING agonists, and delivery of these STING agonists either by conjugation or liposomes/nanoparticles. Considering there have been a great number of reports regarding nanosystem-aided delivery, here, we examine the development of STING agonists, especially for non-CDNs and their delivery specifically by conjugation strategy, with a focus on the STING agonists in clinical trials and current challenges of their potential in cancer immunotherapy.
ISSN:2162-2531