In vitro-transcribed RNAs are emerging as new biologics for therapeutic innovation, as exemplified by their application recently in SARS-CoV-2 vaccinations. RNAs prepared by in vitro transcription (IVT) allow transient expression of proteins of interest, conferring safety over DNA- or virus-mediated gene delivery systems. However, in vitro-transcribed RNAs should be used with caution because of their immunogenicity, which is in part triggered by double-stranded RNA (dsRNA) byproducts during IVT. Cellular innate immune response to dsRNA byproducts can lead to undesirable consequences, including suppression of protein synthesis and cell death, which in turn can detrimentally impact the efficacy of mRNA therapy. Thus, it is critical to understand the nature of IVT byproducts and the mechanisms by which they trigger innate immune responses.

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体外转录 RNA 的免疫原性

体外转录的 RNA 正在成为治疗创新的新生物制剂，最近它们在 SARS-CoV-2 疫苗接种中的应用就是例证。通过体外转录 (IVT)制备的 RNA允许感兴趣的蛋白质的瞬时表达，赋予 DNA 或病毒介导的基因传递系统的安全性。然而，体外应谨慎使用转录的 RNA，因为它们具有免疫原性，这部分是由 IVT 期间的双链 RNA (dsRNA) 副产物触发的。对 dsRNA 副产物的细胞先天免疫反应可导致不良后果，包括抑制蛋白质合成和细胞死亡，这反过来又会对 mRNA 治疗的功效产生不利影响。因此，了解 IVT 副产物的性质以及它们触发先天免疫反应的机制至关重要。