Abstract：
While mRNA vaccines have shown their worth, they have the same failing as inactivated vaccines, namely they have limited half-life, are non-replicating, and therefore limited to the size of the vaccine payload for the amount of material translated. New advances averting these problems are combining replicon RNA (RepRNA) technology with nanotechnology. RepRNA are large self-replicating RNA molecules (typically 12-15 kb) derived from viral genomes defective in at least one essential structural protein gene. They provide sustained antigen production, effectively increasing vaccine antigen payloads over time, without the risk of producing infectious progeny. The major limitations with RepRNA are RNase-sensitivity and inefficient uptake by dendritic cells (DCs), which need to be overcome for efficacious RNA-based vaccine design. We employed biodegradable delivery vehicles to protect the RepRNA and promote DC delivery. Condensing RepRNA with polyethylenimine (PEI) and encapsulating RepRNA into novel Coatsome-replicon vehicles are two approaches that have proven effective for delivery to DCs and induction of immune responses in vivo.
摘要：
虽然mRNA疫苗已经显示出它们的价值，它们和灭活疫苗一样失败，即它们的半衰期有限，是不可复制的，并且因此限于翻译的材料量的疫苗有效载荷的大小。避免这些问题的新进展是将复制子RNA（RepRNA）技术与纳米技术相结合。RepRNA是源自至少一种必需结构蛋白基因缺陷的病毒基因组的大的自我复制RNA分子(通常12-15kb)。它们提供持续的抗原生产，随着时间的推移有效增加疫苗抗原有效载荷，没有产生传染性后代的风险。RepRNA的主要限制是RNA酶敏感性和树突状细胞（DC）的低效摄取，这需要克服有效的基于RNA的疫苗设计。我们采用可生物降解的递送载体来保护RepRNA并促进DC递送。将RepRNA与聚乙烯亚胺（PEI）缩合并将RepRNA封装到新型包被体复制子载体中是两种已被证明有效递送至DC和诱导体内免疫应答的方法。
