Rapid Surface Display of mRNA Antigens by Bacteria-Derived Outer Membrane Vesicles for a Personalized Tumor Vaccine

Yao Li, Xiaotu Ma, Yale Yue, Kaiyue Zhang, Keman Cheng, Qingqing Feng, Nana Ma, Jie Liang, Tianjiao Zhang, Lizhuo Zhang, Zhiqiang Chen, Xinwei Wang, Lei Ren, Xiao Zhao, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

Abstract

Therapeutic mRNA vaccination is an attractive approach to trigger antitumor immunity. However, the mRNA delivery technology for customized tumor vaccine is still limited. In this work, bacteria-derived outer membrane vesicles (OMVs) are employed as an mRNA delivery platform by genetically engineering with surface decoration of RNA binding protein, L7Ae, and lysosomal escape protein, listeriolysin O (OMV-LL). OMV-LL can rapidly adsorb box C/D sequence-labelled mRNA antigens through L7Ae binding (OMV-LL-mRNA) and deliver them into dendritic cells (DCs), following by the cross-presentation via listeriolysin O-mediated endosomal escape. OMV-LL-mRNA significantly inhibits melanoma progression and elicits 37.5% complete regression in a colon cancer model. OMV-LL-mRNA induces a long-term immune memory and protects the mice from tumor challenge after 60 days. In summary, this platform provides a delivery technology distinct from lipid nanoparticles (LNPs) for personalized mRNA tumor vaccination, and with a “Plug-and-Display” strategy that enables its versatile application in mRNA vaccines.

Original languageEnglish (US)
Article number2109984
JournalAdvanced Materials
Volume34
Issue number20
DOIs
StatePublished - May 19 2022

Keywords

  • RNA binding protein
  • box C/D
  • cancer immunotherapy
  • mRNA vaccines
  • outer membrane vesicles
  • rapid display

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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