DataVXAdvanced MaterialsPaper
journal article·2023-01

An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy

Pei Huang, Lingsheng Jiang, Hui Pan, Lingwen Ding, Bo Zhou, Mengyao Zhao, Jianhua Zou, Benhao Li, Meiwei Qi, Hongzhang Deng, Yongfeng Zhou, Xiaoyuan Chen

Advanced Materials· Volume 35· Issue 3
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Source abstract

Abstract

Abstract Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are the most clinically advanced but they require cumbersome four components and suffer from inflammation‐related side effects that should be minimized for safety. Yet, a certain level of proinflammatory responses and innate immune activation are required to evoke T‐cell immunity for mRNA cancer vaccination. To address these issues and develop potent yet low‐inflammatory mRNA cancer vaccine vectors, a series of alternating copolymers “PHTA” featured with ortho‐hydroxy tertiary amine (HTA) repeating units for mRNA delivery is synthesized, which can play triple roles of condensing mRNA, enhancing the polymeric nanoparticle (PNP) stability, and prolonging circulation time. Unlike LNPs exhibiting high levels of inflammation, the PHTA‐based PNPs show negligible inflammatory side effects in vivo. Importantly, the top candidate PHTA‐C18 enables successful mRNA cancer vaccine delivery in vivo and leads to a robust CD8+ T cell mediated antitumor cellular immunity. Such PHTA‐based integrated PNP provides a potential approach for establishing mRNA cancer vaccines with good inflammatory safety profiles.
Source: crossref · Quality: baseline

Research context

PolymersNanomaterials

OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · Virus-based gene therapy research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules Shanghai Jiao Tong University Shanghai 200240 China

Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and Faculty of Engineering National University of Singapore Singapore 119074 Singapore

Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

Department of Pathology Yong Loo Lin School of Medicine National University of Singapore Singapore 119074 Singapore

Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore

Institute of Molecular and Cell Biology Agency for Science Technology, and Research (A*STAR) 61 Biopolis Drive, Proteos Singapore 138673 Singapore

Funding

National Natural Science Foundation of China

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