STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy.
Lei ZhouWenzhe YiZehong ZhangXiaoting ShanZitong ZhaoXiangshi SunJue WangHao WangHualiang JiangMingyue ZhengDangge WangYaping LiPublished in: National science review (2023)
Messenger RNA (mRNA) vaccine is revolutionizing the methodology of immunization in cancer. However, mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport, rapid clearance, catalytic hydrolysis, insufficient cellular entry and endosome entrapment. Herein, we design a mRNA nanovaccine based on intelligent design to overcome these obstacles. Highly efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers, ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) to targets. It activates stimulator of interferon genes (STING), promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo , thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing mice. This work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization, with great translational potential for enhancing cancer immunotherapy.
Keyphrases
- highly efficient
- binding protein
- machine learning
- type diabetes
- signaling pathway
- squamous cell carcinoma
- metabolic syndrome
- drug delivery
- immune response
- genome wide
- young adults
- insulin resistance
- cancer therapy
- artificial intelligence
- climate change
- drug release
- human health
- big data
- protein kinase
- crystal structure