文章：

用于疫苗和免疫疗法的下一代自我复制RNA载体

Next generation self-replicating RNA vectors for vaccines and immunotherapies 

原文发布日期：2022-02-22 

英文摘要：

RNA technology has recently come to the forefront of innovative medicines and is being explored for a wide range of therapies, including prophylactic and therapeutic vaccines, biotherapeutic protein expression and gene therapy. In addition to conventional mRNA platforms now approved for prophylactic SARS-CoV2 vaccines, synthetic self-replicating RNA vaccines are currently being evaluated in the clinic for infectious disease and oncology. The prototypical srRNA vectors in clinical development are derived from alphaviruses, specifically Venezuelan Equine Encephalitis Virus (VEEV). While non-VEEV alphaviral strains have been explored as single cycle viral particles, their use as synthetic vectors largely remains under-utilized in clinical applications. Here we describe the potential commonalities and differences in synthetic alphaviral srRNA vectors in host cell interactions, immunogenicity, cellular delivery, and cargo expression. Thus, unlike the current thinking that VEEV-based srRNA is a one-size-fits-all platform, we argue that a new drug development approach leveraging panels of customizable, synthetic srRNA vectors will be required for clinical success. 

摘要翻译： 

RNA技术近年来已成为创新药物的前沿领域，其应用范围正被拓展至多种疗法，包括预防性和治疗性疫苗、生物治疗性蛋白表达及基因治疗。除目前已获批用于预防性SARS-CoV2疫苗的传统mRNA平台外，合成型自我复制RNA疫苗正在临床研究中针对传染病和肿瘤学领域进行评估。临床开发中的原型自我复制RNA载体源自甲病毒，特别是委内瑞拉马脑炎病毒（VEEV）。虽然非VEEV甲病毒毒株已被探索作为单周期病毒颗粒使用，但其作为合成载体在临床应用中的潜力尚未被充分挖掘。本文阐述了合成甲病毒自我复制RNA载体在宿主细胞相互作用、免疫原性、细胞递送和载荷表达方面可能存在的共性与差异。因此，与当前认为基于VEEV的自我复制RNA是通用平台的观念不同，我们认为需要采用一种利用可定制合成自我复制RNA载体组合的新药开发策略才能取得临床成功。

原文链接：

Next generation self-replicating RNA vectors for vaccines and immunotherapies