Curated Papers > Recent high-impact research on "mRNA vaccines" (IF≥30, last 5 years)

Nanotechnology-based mRNA vaccines.

Literature Information

DOI	10.1038/s43586-023-00246-7
PMID	40747084
Journal	Nature reviews. Methods primers
Impact Factor	56.0
JCR Quartile	Q1
Publication Year	2023
Times Cited	15
Keywords	mRNA vaccines, nanotechnology, immune response, drug delivery, biomaterials
Literature Type	Journal Article
ISSN	2662-8449
Issue	3(1)
Authors	Shuying Chen, Xiangang Huang, Yonger Xue, Ester Álvarez-Benedicto, Yesi Shi, Wei Chen, Seyoung Koo, Daniel J Siegwart, Yizhou Dong, Wei Tao

TL;DR

This research highlights the transformative potential of mRNA vaccines in combating infectious diseases and cancers, emphasizing their advantages over traditional vaccines, such as rapid design and high efficacy. It also addresses the significant challenges of mRNA delivery, proposing a modular nanotechnology approach to improve stability, cellular uptake, and immune response, while outlining key manufacturing parameters and future directions for clinical applications.

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mRNA vaccines · nanotechnology · immune response · drug delivery · biomaterials

Abstract

mRNA vaccines have emerged as a revolutionary tool to generate rapid and precise immune responses against infectious diseases and cancers. Compared with conventional vaccines such as inactivated viruses, viral vectors, protein subunits or DNA-based vaccines, mRNA vaccines stand out owing to multiple advantages, including simplicity of design, fast production, enhanced safety and high efficacy. Nevertheless, efficient and targeted delivery of mRNA molecules remains a significant challenge owing to their inherent instability and susceptibility to degradation. Nanotechnology offers innovative solutions to surmount these obstacles and amplify the potency of mRNA vaccines. This Primer aims to outline a modular approach to developing biomaterials and nanotechnology for mRNA vaccines, with a focus on particle design, formulation evaluation and therapeutic applications. We delve into the underlying mechanisms of nanoparticle-facilitated mRNA protection, cellular uptake, endosomal escape and immune stimulation. We underscore the critical parameters that impact the manufacturing and clinical implementation of nanomaterial-based mRNA vaccines. Finally, we present the current limitations and future perspectives in the advancement of nanotechnology-enhanced mRNA vaccines for broad applications in prophylactic and therapeutic interventions.

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Primary Questions Addressed

1. What are the specific types of nanoparticles being used in the formulation of mRNA vaccines, and how do they enhance vaccine stability?
2. How do the mechanisms of cellular uptake and endosomal escape differ among various nanocarrier systems for mRNA delivery?
3. What are the current clinical trials or studies investigating the efficacy of nanotechnology-based mRNA vaccines in treating specific cancers or infectious diseases?
4. In what ways can the modular approach to developing biomaterials for mRNA vaccines be applied to other therapeutic areas beyond vaccines?
5. What are the regulatory challenges faced in the clinical implementation of nanomaterial-based mRNA vaccines, and how can they be addressed?

Key Findings

Research Background and Purpose

mRNA vaccines have gained prominence as a transformative approach for eliciting rapid and precise immune responses against infectious diseases and cancers. Unlike traditional vaccine modalities, mRNA vaccines offer advantages such as straightforward design, rapid production, improved safety profiles, and high efficacy. However, the effective and targeted delivery of mRNA remains a major challenge due to the molecules' instability and susceptibility to degradation. This Primer aims to present a modular strategy for utilizing biomaterials and nanotechnology to enhance the development and efficacy of mRNA vaccines.

Main Methods/Materials/Experimental Design

The research employs a comprehensive framework to investigate the role of nanotechnology in the development of mRNA vaccines. The following flowchart illustrates the key components of the study:

The research emphasizes several critical aspects:

• Nanoparticle Design: Focuses on creating nanoparticles that can effectively encapsulate mRNA.
• Formulation Evaluation: Involves assessing the stability, release profile, and bioavailability of the mRNA-loaded nanoparticles.
• Therapeutic Applications: Investigates various applications of the developed mRNA vaccines in preventive and therapeutic settings.
• Mechanisms of Action: Explores how nanoparticles facilitate mRNA protection, enhance cellular uptake, promote endosomal escape, and stimulate immune responses.

Key Results and Findings

The study highlights several important findings:

• Nanoparticles can significantly enhance the stability and delivery efficiency of mRNA vaccines.
• Effective encapsulation of mRNA within nanoparticles leads to improved cellular uptake and endosomal escape.
• The immune stimulation potential of mRNA vaccines can be augmented through strategic nanoparticle design.
• Critical parameters such as manufacturing processes and clinical implementation strategies play a vital role in the success of nanomaterial-based mRNA vaccines.

Main Conclusions/Significance/Innovativeness

The Primer concludes that the integration of nanotechnology in mRNA vaccine development represents a promising avenue for overcoming existing delivery challenges. The innovative use of nanoparticles not only enhances the stability and efficacy of mRNA vaccines but also opens up new therapeutic possibilities in both prophylactic and therapeutic contexts. This research underscores the importance of a modular approach in developing mRNA vaccines, highlighting the potential for significant advancements in vaccine technology.

Research Limitations and Future Directions

While the findings are promising, the study acknowledges several limitations:

• The complexity of manufacturing nanomaterials for mRNA delivery remains a challenge.
• There is a need for further research on the long-term safety and efficacy of nanotechnology-enhanced mRNA vaccines in diverse populations.

Future directions include:

• Exploring new materials and designs for nanoparticles to improve mRNA stability and delivery.
• Conducting extensive clinical trials to evaluate the safety and efficacy of these advanced mRNA vaccines.
• Investigating the potential of combining mRNA vaccines with other therapeutic modalities for enhanced outcomes.

References

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Literatures Citing This Work

1. Blood-brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system. - Chang Wang;Yonger Xue;Tamara Markovic;Haoyuan Li;Siyu Wang;Yichen Zhong;Shi Du;Yuebao Zhang;Xucheng Hou;Yang Yu;Zhengwei Liu;Meng Tian;Diana D Kang;Leiming Wang;Kaiyuan Guo;Dinglingge Cao;Jingyue Yan;Binbin Deng;David W McComb;Ramon E Parsons;Angelica M Minier-Toribio;Leanne M Holt;Jiayi Pan;Alice Hashemi;Brian H Kopell;Alexander W Charney;Eric J Nestler;Paul C Peng;Yizhou Dong - Nature materials (2025)
2. Developing mRNA Nanomedicines with Advanced Targeting Functions. - Ji Wang;Lijun Cai;Ning Li;Zhiqiang Luo;Haozhen Ren;Bing Zhang;Yuanjin Zhao - Nano-micro letters (2025)
3. RNA chemistry and therapeutics. - Siyu Wang;Drew Weissman;Yizhou Dong - Nature reviews. Drug discovery (2025)
4. Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity. - Ningqiang Gong;Dongyoon Kim;Mohamad-Gabriel Alameh;Rakan El-Mayta;Emily L Han;Garima Dwivedi;Rohan Palanki;Qiangqiang Shi;Xuexiang Han;Lulu Xue;Junchao Xu;Zilin Meng;Tianyu Luo;Christian G Figueroa-Espada;Drew Weissman;Jinghong Li;Michael J Mitchell - Nature biomedical engineering (2025)
5. Advances and Strategies in Enhancing mRNA Cancer Vaccines. - Miao Zhang;Shengqi Chen;Haijun Hu;Yenhui Ong;Qianqian Ni - Advanced materials (Deerfield Beach, Fla.) (2025)
6. Systemic reprogramming of tumour immunity via IL-10-mRNA nanoparticles. - Chuang Liu;Xiangang Huang;Kok-Siong Chen;Sihan Xiong;Alexey V Yaremenko;Xueyan Zhen;Xinru You;Filippo Rossignoli;Yi Tang;Seyoung Koo;Wei Chen;Na Kong;Tian Xie;Khalid Shah;Wei Tao - Nature nanotechnology (2025)
7. Homologous heteropolyaromatic covalent organic frameworks for enhancing photocatalytic hydrogen peroxide production and aerobic oxidation. - Jiani Yang;Zhenyang Zhao;Xu Liu;Heng Yang;Jin Yang;Mi Zhou;Shuang Li;Xikui Liu;Xiaohui Xu;Chong Cheng - Nature communications (2025)
8. Cryomicroneedle Arrays for Biotherapeutics Delivery. - Chunli Yang;Li Zhang;Angxi Zhou;Siyi Wang;Ya Ren;Maya Xiang;Run Tian;Yang Yu;Rong Li;Maling Gou - Small science (2025)
9. Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions. - Jiajun Zhu;Jianming Zhou;Yiting Tang;Ruotong Huang;Chengjia Lu;Ke Qian;Qingyu Zhou;Jingjun Zhang;Xiaoyi Yang;Wenhan Zhou;Jiaqiang Wu;Qiudan Chen;Yong Lin;Shuying Chen - Cancer cell international (2025)
10. Mechanism of RCD and the Role of Different Death Signaling Pathways in Cancer. - Jianming Zhou;Ruotong Huang;Maidinai Aimaiti;Qingyu Zhou;Xiang Wu;Jiajun Zhu;Xiangyi Ma;Ke Qian;Qi Zhou;Lianlong Hu;Xiaoyi Yang;Yiting Tang;Yong Lin;Shuying Chen - Biomedicines (2025)

... (5 more literatures)

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