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.
信使核糖核酸（mRNA）疫苗正在彻底改变癌症免疫接种的方法。然而，mRNA免疫接种受到多重生物屏障的严重限制，包括淋巴转运效率低、快速清除、催化水解、细胞进入不足以及内体滞留等问题。为此，我们基于智能设计构建了一种mRNA纳米疫苗以克服这些障碍。通过机器学习技术从多种纳米载体的数据集中筛选出高效纳米疫苗，确保mRNA抗原和环磷酸鸟苷-腺苷酸（cGAMP）成功递送至靶点。该疫苗能激活干扰素基因刺激因子（STING），促进mRNA编码抗原的呈递，增强体内抗肿瘤免疫，从而抑制肿瘤生长并确保荷瘤小鼠长期存活。本研究为促进STING激动剂协同的mRNA免疫接种提供了一种可行且安全的策略，在增强癌症免疫治疗方面具有巨大的转化潜力。
肿瘤(癌症)患者之家