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

doi:10.1002/adma.202109984

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 journal › Article › peer-review

135 Scopus citations

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 language	English (US)
Article number	2109984
Pages (from-to)	e2109984
Journal	Advanced Materials
Volume	34
Issue number	20
DOIs	https://doi.org/10.1002/adma.202109984
State	Published - May 19 2022

Keywords

RNA binding protein
box C/D
cancer immunotherapy
mRNA vaccines
outer membrane vesicles
rapid display
Nanoparticles
Animals
Cancer Vaccines/genetics
Bacteria
Mice
Liposomes
RNA, Messenger

ASJC Scopus subject areas

Mechanics of Materials
Mechanical Engineering
Materials Science(all)

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

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.",

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

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T1 - Rapid Surface Display of mRNA Antigens by Bacteria-Derived Outer Membrane Vesicles for a Personalized Tumor Vaccine

AU - Li, Yao

AU - Ma, Xiaotu

AU - Yue, Yale

AU - Zhang, Kaiyue

AU - Cheng, Keman

AU - Feng, Qingqing

AU - Ma, Nana

AU - Liang, Jie

AU - Zhang, Tianjiao

AU - Zhang, Lizhuo

AU - Chen, Zhiqiang

AU - Wang, Xinwei

AU - Ren, Lei

AU - Zhao, Xiao

AU - Nie, Guangjun

PY - 2022/5/19

Y1 - 2022/5/19

N2 - 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.

AB - 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.

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KW - Mice

KW - Liposomes

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

Abstract

Keywords

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