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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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| 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. |
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| ISSN: | 2162-2531 |