One-component ionizable amphiphilic Janus dendrimers as a delivery platform for efficient mRNA vaccine development

There have been rapid advances in nucleoside-modified messenger RNA-based
vaccines, particularly during the SARS-CoV2 pandemic, demonstrating a
rapid and cost-effective approach for addressing infectious diseases. A
major challenge remains in developing a delivery system that protects mRNA
from degradation and facilitates its passage through tissue and cellular
barriers. Current four-component lipid nanoparticles enable efficient
endosomal escape and are a pivotal technology for the delivery of mRNA
vaccines. However, challenges such as stability, availability, durability,
and adverse effects persist. We have developed a self-assembling
one-component ionizable amphiphilic Janus dendrimers (IAJD) delivery
system with naturally occurring amino heads, capable of efficiently
delivering mRNA to the spleen and lymph nodes.  This
single-component system simplifies synthesis, reduces development
complexity, and enable rapid global distribution of mRNA vaccines during
pandemics. As a proof of concept, one-component IAJD97, formulated with
mRNA encoding norovirus mRNA capsid protein, demonstrates the potential of
IAJDs as efficient delivery platform for mRNA vaccines, advancing their
effectiveness and expanding applications to improve public health
outcomes.

经核苷修饰的信使核糖核酸（messenger RNA, mRNA）疫苗领域近年来取得快速进展，尤其在严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）大流行期间，该类疫苗为应对传染病提供了快速且高性价比的解决方案。当前仍存在一项核心挑战：亟需开发可保护mRNA免于降解，并协助其穿越组织与细胞屏障的递送系统。目前广泛应用的四组分脂质纳米颗粒可实现高效内体逃逸，是mRNA疫苗递送的关键技术，但仍存在稳定性、可及性、持久性以及不良反应等诸多问题。本研究团队开发了一种自组装单组分可电离两亲性贾纳斯树状大分子（ionizable amphiphilic Janus dendrimers, IAJD）递送系统，其头部采用天然存在的氨基酸基团，可高效将mRNA递送至脾脏与淋巴结。该单组分系统简化了合成流程，降低了开发复杂度，能够助力大流行期间mRNA疫苗在全球范围内的快速分发。作为概念验证，搭载编码诺如病毒衣壳蛋白mRNA的单组分IAJD97制剂，证实了IAJD作为高效mRNA疫苗递送平台的潜力，可提升疫苗有效性并拓展应用场景，进而改善公共卫生结局。