Recently, chemically synthesized minimal mRNA (CmRNA) has emerged as a promising alternative to in vitro transcribed mRNA (IVT-mRNA) for cancer therapy and immunotherapy. CmRNA lacking the untranslated regions and polyadenylation exhibits enhanced stability and efficiency. Encapsulation of CmRNA within lipid-polymer hybrid nanoparticles (LPPs) offers an effective approach for personalized neoantigen mRNA vaccines with improved control over tumor growth. LPP-based delivery systems provide superior pharmacokinetics, stability, and lower toxicity compared to viral vectors, naked mRNA, or lipid nanoparticles that are commonly used for mRNA delivery. Precise customization of LPPs in terms of size, surface charge, and composition allows for optimized cellular uptake, target specificity, and immune stimulation. CmRNA-encoded neo-antigens demonstrate high translational efficiency, enabling immune recognition by CD8⁺ T cells upon processing and presentation. This perspective highlights the potential benefits, challenges, and future directions of CmRNA neoantigen vaccines in cancer therapy compared to Circular RNAs and IVT-mRNA. Further research is needed to optimize vaccine design, delivery, and safety assessment in clinical trials. Nevertheless, personalized LPP-CmRNA vaccines hold great potential for advancing cancer immunotherapy, paving the way for personalized medicine.

最近，化学合成的最小 mRNA (CmRNA) 已成为体外转录 mRNA (IVT-mRNA) 的有前途的替代品，用于癌症治疗和免疫治疗。缺乏非翻译区和聚腺苷酸化的 CmRNA 表现出增强的稳定性和效率。将 CmRNA 封装在脂质聚合物杂化纳米颗粒 (LPP) 中，为个性化新抗原 mRNA 疫苗提供了一种有效的方法，可改善对肿瘤生长的控制。与常用于 mRNA 递送的病毒载体、裸 mRNA 或脂质纳米粒子相比，基于 LPP 的递送系统具有优异的药代动力学、稳定性和较低的毒性。LPP 在尺寸、表面电荷和成分方面的精确定制可以优化细胞摄取、靶标特异性和免疫刺激。CmRNA 编码的新抗原表现出高翻译效率，使得 CD8 ⁺ T 细胞在处理和呈递时能够进行免疫识别。这一观点强调了与环状 RNA 和 IVT-mRNA 相比，CmRNA 新抗原疫苗在癌症治疗中的潜在益处、挑战和未来方向。需要进一步研究来优化临床试验中的疫苗设计、交付和安全性评估。尽管如此，个性化 LPP-CmRNA 疫苗在推进癌症免疫治疗方面具有巨大潜力，为个性化医疗铺平道路。