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文献精选 > 近年高分"mRNA疫苗"研究（IF≥30，近5年）

mRNA vaccine: a potential therapeutic strategy. ​

文献信息 ​

DOI10.1186/s12943-021-01311-z
PMID33593376
期刊Molecular cancer
影响因子33.9
JCR 分区Q1
发表年份2021
被引次数190
关键词抗体依赖性增强, COVID-19 mRNA疫苗, 临床试验, 递送策略, 树突状细胞靶向
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1476-4598
页码33
期号20(1)
作者Yang Wang, Ziqi Zhang, Jingwen Luo, Xuejiao Han, Yuquan Wei, Xiawei Wei

一句话小结 ​

本研究探讨了mRNA疫苗在癌症和病毒性疾病防治中的潜力，强调了通过序列优化和递送策略提高其安全性和有效性。研究结果表明，结合免疫学原理和新型递送方法可增强mRNA疫苗的抗原反应性，为应对COVID-19及其他疾病提供了重要的临床应用基础。

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抗体依赖性增强 · COVID-19 mRNA疫苗 · 临床试验 · 递送策略 · 树突状细胞靶向

摘要 ​

mRNA疫苗在癌症和病毒性疾病的防治中具有巨大的潜力，因其在安全性、有效性和工业生产方面的优势。在过去几十年中，我们见证了通过序列优化开发出不同种类的mRNA，以克服过度的mRNA免疫原性、不稳定性和低效性等缺点。基于免疫学研究，mRNA疫苗与免疫佐剂及各种递送策略相结合。除了序列优化外，mRNA递送策略的辅助也是稳定mRNA并提高其有效性的另一种方法。对提高抗原反应性的理解深入了mRNA诱导的先天免疫和适应性免疫，而不依赖于抗体依赖的增强活性。因此，为了解决这一问题，科学家们进一步开发了基于载体的mRNA疫苗（脂质递送、聚合物递送、肽递送、类病毒复制颗粒和阳离子纳米乳），裸mRNA疫苗以及基于树突状细胞的mRNA疫苗。本文将讨论mRNA疫苗的分子生物学及其抗病毒和抗肿瘤机制，介绍其免疫学现象、递送策略，以及它们在2019冠状病毒病（COVID-19）和针对癌症及病毒性疾病的相关临床试验中的重要性。最后，我们将讨论mRNA疫苗在应对细菌和寄生虫疾病方面的挑战。

英文摘要 ​

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

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主要研究问题 ​

  1. mRNA疫苗在癌症治疗中的具体应用有哪些？它们与传统疗法相比的优势是什么？
  2. 除了病毒性疾病，mRNA疫苗在细菌和寄生虫疾病中的潜在应用和挑战是什么？
  3. 目前有哪些临床试验正在评估mRNA疫苗在抗肿瘤治疗中的有效性？
  4. 如何通过改进mRNA递送策略来提高疫苗的稳定性和免疫反应？
  5. mRNA疫苗在新冠病毒疫苗研发中的成功经验可以如何转化到其他疾病的疫苗开发中？

核心洞察 ​

研究背景和目的 ​

mRNA疫苗在癌症和病毒性疾病的治疗中展现出巨大的潜力，因其在安全性、有效性和工业生产方面的优势。尽管近年来在mRNA疫苗的研究中取得了显著进展，但仍面临着免疫原性过强、稳定性差和传递效率低等问题。因此，本研究旨在探讨mRNA疫苗的分子生物学特征、抗病毒和抗肿瘤机制，以及其在COVID-19和相关临床试验中的应用。

主要方法/材料/实验设计 ​

研究采用文献综述的方法，系统分析mRNA疫苗的不同类型及其传递策略，重点关注以下几个方面：

  1. mRNA疫苗分类：
    • 自我扩增RNA (saRNA)
    • 非复制mRNA
  2. 交付策略：
    • 脂质纳米颗粒 (LNPs)
    • 聚合物基传递
    • 肽基传递
    • 病毒样复制粒子
    • 阳离子纳米乳
    • 裸mRNA疫苗
  3. 免疫机制：
    • 增强抗原反应性
    • 诱导先天和适应性免疫
Mermaid diagram

关键结果和发现 ​

  1. mRNA疫苗的优势：

    • 安全性高，未见基因组整合和抗生素耐药性。
    • 可通过修改mRNA序列和采用不同的传递系统提高稳定性和有效性。
    • 疫苗能够诱导强烈的抗体和细胞免疫反应。

  2. 临床试验结果：

    • COVID-19疫苗的临床试验显示出良好的安全性和免疫原性。
    • 针对癌症的mRNA疫苗在多项临床试验中也表现出希望的疗效。

主要结论/意义/创新性 ​

mRNA疫苗技术在癌症和病毒性疾病的治疗中具有重要的应用前景。其通过优化序列、改善传递系统和联合免疫佐剂等策略，显著提高了免疫应答。研究表明，mRNA疫苗不仅能够有效激活先天免疫，还能增强适应性免疫反应，为疫苗的临床应用奠定了基础。

研究局限性和未来方向 ​

尽管mRNA疫苗展现出良好的应用前景，但仍存在一些局限性：

  • 免疫原性问题：mRNA疫苗的免疫原性可能导致过度的免疫反应。
  • 稳定性问题：mRNA在体内的稳定性仍需进一步提高。

未来的研究方向包括：

  • 进一步优化mRNA的化学修饰和传递系统。
  • 扩展mRNA疫苗在细菌和寄生虫疾病中的应用研究。
  • 进行更大规模的临床试验，以验证其在不同人群中的有效性和安全性。

参考文献 ​

  1. CD133 mRNA-Loaded Dendritic Cell Vaccination Abrogates Glioma Stem Cell Propagation in Humanized Glioblastoma Mouse Model. - Angelique Sao-Mai Sy Do;Takayuki Amano;Lincoln A Edwards;Lei Zhang;Mariza De Peralta-Venturina;John S Yu - Molecular therapy oncolytics (2020)
  2. Role of 5'- and 3'-untranslated regions of mRNAs in human diseases. - Sangeeta Chatterjee;Jayanta K Pal - Biology of the cell (2009)
  3. A COVID-19 mRNA vaccine encoding SARS-CoV-2 virus-like particles induces a strong antiviral-like immune response in mice. - Jing Lu;Guoliang Lu;Shudan Tan;Jia Xia;Hualong Xiong;Xiaofei Yu;Qingqing Qi;Xiang Yu;Li Li;Hang Yu;Ningshao Xia;Tianying Zhang;Yingjie Xu;Jinzhong Lin - Cell research (2020)
  4. Microinjection of rabbit hemoglobin messenger RNA into amphibian oocytes and embryos. - J Brachet;G Huez;E Hubert - Proceedings of the National Academy of Sciences of the United States of America (1973)
  5. The combination of 4-1BBL and CD40L strongly enhances the capacity of dendritic cells to stimulate HIV-specific T cell responses. - Brenda De Keersmaecker;Carlo Heirman;Jurgen Corthals;Christophe Empsen;Leo A van Grunsven;Sabine D Allard;Joeri Pen;Patrick Lacor;Kris Thielemans;Joeri L Aerts - Journal of leukocyte biology (2011)
  6. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. - D Boczkowski;S K Nair;D Snyder;E Gilboa - The Journal of experimental medicine (1996)
  7. mRNA-Lipoplex loaded microbubble contrast agents for ultrasound-assisted transfection of dendritic cells. - Marie-Luce De Temmerman;Heleen Dewitte;Roosmarijn E Vandenbroucke;Bart Lucas;Claude Libert;Jo Demeester;Stefaan C De Smedt;Ine Lentacker;Joanna Rejman - Biomaterials (2011)
  8. Challenges and advances towards the rational design of mRNA vaccines. - Charlotte Pollard;Stefaan De Koker;Xavier Saelens;Guido Vanham;Johan Grooten - Trends in molecular medicine (2013)
  9. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. - Yi Yang;Chia-Wei Li;Li-Chuan Chan;Yongkun Wei;Jung-Mao Hsu;Weiya Xia;Jong-Ho Cha;Junwei Hou;Jennifer L Hsu;Linlin Sun;Mien-Chie Hung - Cell research (2018)
  10. GM-CSF and IL-4 induce dendritic cell differentiation and disrupt osteoclastogenesis through M-CSF receptor shedding by up-regulation of TNF-alpha converting enzyme (TACE). - Masahiro Hiasa;Masahiro Abe;Ayako Nakano;Asuka Oda;Hiroe Amou;Shinsuke Kido;Kyoko Takeuchi;Kumiko Kagawa;Kenichiro Yata;Toshihiro Hashimoto;Shuji Ozaki;Kenzo Asaoka;Eiji Tanaka;Keiji Moriyama;Toshio Matsumoto - Blood (2009)

引用本文的文献 ​

  1. Vaccination hesitancy and the "myth" on mRNA-based vaccines in Italy in the COVID-19 era: Does urgency meet major safety criteria? - Salvatore Chirumbolo - Journal of medical virology (2021)
  2. Editorial: mRNA Vaccines and Future Epidemic, Pandemic, and Endemic Zoonotic Virus Infections. - Dinah V Parums - Medical science monitor : international medical journal of experimental and clinical research (2021)
  3. Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. - Dinah V Parums - Medical science monitor : international medical journal of experimental and clinical research (2021)
  4. Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer. - Margaux Saillard;Mara Cenerenti;Pedro Romero;Camilla Jandus - Vaccines (2021)
  5. Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2. - Javier T Granados-Riveron;Guillermo Aquino-Jarquin - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2021)
  6. Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2. - Marco Palma - Germs (2021)
  7. Vaccine design and delivery approaches for COVID-19. - Kiana Shahzamani;Fatemeh Mahmoudian;Shahrzad Ahangarzadeh;Mohammad Mehdi Ranjbar;Leila Beikmohammadi;Samira Bahrami;Elmira Mohammadi;Sahar Esfandyari;Abbas Alibakhshi;Shaghayegh Haghjooy Javanmard - International immunopharmacology (2021)
  8. Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine. - Hua Zhong;Shuai Liu;Fang Cao;Yi Zhao;Jianguo Zhou;Feng Tang;Zhaohua Peng;Yangsheng Li;Shen Xu;Chunlin Wang;Guohua Yang;Zhi-Qiang Li - Frontiers in immunology (2021)
  9. Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency. - Sun Chang Kim;Simranjeet Singh Sekhon;Woo-Ri Shin;Gna Ahn;Byung-Kwan Cho;Ji-Young Ahn;Yang-Hoon Kim - Molecular & cellular toxicology (2022)
  10. Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2. - Daniela Calina;Antonio F Hernández;Thomas Hartung;Alexey M Egorov;Boris Nikolaevich Izotov;Taxiarchis Konstantinos Nikolouzakis;Aristidis Tsatsakis;Panayiotis G Vlachoyiannopoulos;Anca Oana Docea - Life (Basel, Switzerland) (2021)

... (180 更多 篇文献)

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