非病毒载体递送自我扩增 RNA 疫苗。
Nonviral delivery of self-amplifying RNA vaccines.
机构信息
Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14604-9. doi: 10.1073/pnas.1209367109. Epub 2012 Aug 20.
Abstract
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
摘要
尽管针对核酸疫苗的研究和开发已经超过了二十年，但仍然没有商业化的产品用于人体。利用最近在使用脂质纳米颗粒（LNPs）进行系统递送短干扰 RNA（siRNA）方面的创新，我们开发了一种自我扩增 RNA 疫苗。在这里，我们表明，与未形成配方的 RNA 相比，LNPs 封装的 9kb 自我扩增 RNA 的非病毒递送大大提高了免疫原性。这种独特的疫苗技术被发现能够引发广泛、有效和保护性的免疫反应，与病毒递送技术相当，但没有病毒载体的固有局限性。鉴于核酸疫苗的许多积极属性，我们的结果表明，有必要对用于递送自我扩增 RNA 疫苗的非病毒技术进行全面评估。
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