Skip to content

Self-assembled mRNA vaccines.

文献信息

DOI10.1016/j.addr.2020.12.014
PMID33400957
期刊Advanced drug delivery reviews
影响因子17.6
JCR 分区Q1
发表年份2021
被引次数203
关键词COVID-19, 基因递送, 免疫接种, 脂质纳米颗粒, 自组装
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN0169-409X
页码83-112
期号170()
作者Jeonghwan Kim, Yulia Eygeris, Mohit Gupta, Gaurav Sahay

一句话小结

本综述探讨了mRNA疫苗的设计与自组装,强调了材料的物理化学特性及其他关键因素对疫苗接种成功的重要性。研究表明,mRNA疫苗在新冠疫苗开发中展现出巨大潜力,同时推动了基因治疗的发展。

在麦伴科研 (maltsci.com) 搜索更多文献

COVID-19 · 基因递送 · 免疫接种 · 脂质纳米颗粒 · 自组装

摘要

mRNA疫苗已经从一个单纯的好奇对象发展为新冠疫苗的领先者。近年来,RNA技术、疫苗学和纳米技术的进步引发了对安全有效的mRNA治疗药物的关注。在本综述中,我们讨论了mRNA疫苗的设计与自组装。自组装是指个体分子的自发组织,这一过程使得我们能够设计具有可定制特性的纳米颗粒。我们强调了常用于递送mRNA的材料,它们的物理化学特性以及其他相关因素,如mRNA优化、给药途径、细胞命运和免疫激活,这些都是成功进行mRNA疫苗接种的重要考虑因素。我们还审视了目前正在临床试验中的新冠mRNA疫苗。mRNA疫苗已准备好进入临床,在新冠疫苗竞赛中展现出巨大的前景,并推动了基因治疗的边界。

英文摘要

mRNA vaccines have evolved from being a mere curiosity to emerging as COVID-19 vaccine front-runners. Recent advancements in the field of RNA technology, vaccinology, and nanotechnology have generated interest in delivering safe and effective mRNA therapeutics. In this review, we discuss design and self-assembly of mRNA vaccines. Self-assembly, a spontaneous organization of individual molecules, allows for design of nanoparticles with customizable properties. We highlight the materials commonly utilized to deliver mRNA, their physicochemical characteristics, and other relevant considerations, such as mRNA optimization, routes of administration, cellular fate, and immune activation, that are important for successful mRNA vaccination. We also examine the COVID-19 mRNA vaccines currently in clinical trials. mRNA vaccines are ready for the clinic, showing tremendous promise in the COVID-19 vaccine race, and have pushed the boundaries of gene therapy.

麦伴智能科研服务

智能阅读回答你对文献的任何问题,帮助理解文献中的复杂图表和公式
定位观点定位某个观点在文献中的蛛丝马迹
加入知识库完成数据提取,报告撰写等更多高级知识挖掘功能

主要研究问题

  1. 自组装mRNA疫苗在临床试验中表现出的有效性与安全性如何?
  2. 目前有哪些新材料被应用于自组装mRNA疫苗的开发中?
  3. 自组装mRNA疫苗的免疫激活机制与传统疫苗有何不同?
  4. 在自组装mRNA疫苗的设计中,哪些物理化学特性最为关键?
  5. 自组装mRNA疫苗在其他疾病(如癌症、病毒性疾病等)的应用前景如何?

核心洞察

研究背景和目的

自2019年新冠病毒(SARS-CoV-2)爆发以来,mRNA疫苗迅速成为抗击COVID-19的前沿技术。本文综述了mRNA疫苗的设计、自组装过程及其在临床应用中的潜力,重点探讨了如何通过优化材料和递送系统来提高mRNA疫苗的有效性和安全性。

主要方法/材料/实验设计

本研究采用以下方法进行mRNA疫苗的设计和评估:

  1. 自组装技术:通过自组装形成纳米颗粒,能够根据需求调整其物理化学特性。
  2. 材料选择:使用脂质纳米颗粒(LNPs)作为mRNA的递送载体,强调其在保护mRNA免受降解和提高细胞摄取方面的优势。
  3. 免疫激活:研究不同的mRNA结构元素(如5'帽、3'非翻译区和聚A尾)对免疫反应的影响。
  4. 临床试验:评估当前在临床试验中的COVID-19 mRNA疫苗的安全性和有效性。

以下是技术路线的Mermaid代码表示:

Mermaid diagram

关键结果和发现

  1. mRNA疫苗的优势:mRNA疫苗具有较高的安全性和有效性,相较于传统疫苗,能够快速产生针对特定抗原的免疫反应。
  2. 递送系统的影响:LNPs能够显著提高mRNA的细胞摄取率,降低免疫系统的副作用。
  3. 临床数据:Pfizer/BioNTech和Moderna的mRNA疫苗在临床试验中显示出超过90%的有效性,且副作用相对轻微。

主要结论/意义/创新性

mRNA疫苗代表了一种新的疫苗开发模式,能够快速响应新出现的传染病。其自组装技术和材料优化的结合使得mRNA疫苗在免疫治疗领域展现出巨大的潜力,尤其是在针对COVID-19的应用中,推动了疫苗的快速开发和广泛使用。

研究局限性和未来方向

  1. 研究局限性:当前研究主要集中在临床前和早期临床阶段,长期效果和潜在副作用仍需进一步评估。
  2. 未来方向:未来的研究应关注mRNA疫苗在不同疾病中的应用,以及改进递送系统以提高针对特定细胞类型的靶向能力。同时,探索更灵活的存储条件和生产流程,以促进mRNA疫苗的广泛使用。

通过这些努力,mRNA疫苗技术有望在未来的疫苗研发和疾病治疗中发挥更大作用。

参考文献

  1. Vesicles of variable sizes produced by a rapid extrusion procedure. - L D Mayer;M J Hope;P R Cullis - Biochimica et biophysica acta (1986)
  2. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. - Akin Akinc;William Querbes;Soma De;June Qin;Maria Frank-Kamenetsky;K Narayanannair Jayaprakash;Muthusamy Jayaraman;Kallanthottathil G Rajeev;William L Cantley;J Robert Dorkin;James S Butler;Liuliang Qin;Timothy Racie;Andrew Sprague;Eugenio Fava;Anja Zeigerer;Michael J Hope;Marino Zerial;Dinah W Y Sah;Kevin Fitzgerald;Mark A Tracy;Muthiah Manoharan;Victor Koteliansky;Antonin de Fougerolles;Martin A Maier - Molecular therapy : the journal of the American Society of Gene Therapy (2010)
  3. Role of 5'- and 3'-untranslated regions of mRNAs in human diseases. - Sangeeta Chatterjee;Jayanta K Pal - Biology of the cell (2009)
  4. Systemic delivery of factor IX messenger RNA for protein replacement therapy. - Suvasini Ramaswamy;Nina Tonnu;Kiyoshi Tachikawa;Pattraranee Limphong;Jerel B Vega;Priya P Karmali;Pad Chivukula;Inder M Verma - Proceedings of the National Academy of Sciences of the United States of America (2017)
  5. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. - Katalin Karikó;Michael Buckstein;Houping Ni;Drew Weissman - Immunity (2005)
  6. Evolving SAXS versatility: solution X-ray scattering for macromolecular architecture, functional landscapes, and integrative structural biology. - Chris A Brosey;John A Tainer - Current opinion in structural biology (2019)
  7. The Biomolecular Corona of Lipid Nanoparticles for Gene Therapy. - Valentina Francia;Raymond M Schiffelers;Pieter R Cullis;Dominik Witzigmann - Bioconjugate chemistry (2020)
  8. Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system. - F DeRosa;B Guild;S Karve;L Smith;K Love;J R Dorkin;K J Kauffman;J Zhang;B Yahalom;D G Anderson;M W Heartlein - Gene therapy (2016)
  9. Challenges in carrier-mediated intracellular delivery: moving beyond endosomal barriers. - Martin P Stewart;Anna Lorenz;James Dahlman;Gaurav Sahay - Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology (2016)
  10. Structural Components for Amplification of Positive and Negative Strand VEEV Splitzicons. - Anna K Blakney;Paul F McKay;Robin J Shattock - Frontiers in molecular biosciences (2018)

引用本文的文献

  1. Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs. - Shintaro Fumoto;Tsuyoshi Yamamoto;Kazuya Okami;Yuina Maemura;Chisato Terada;Asako Yamayoshi;Koyo Nishida - Pharmaceutics (2021)
  2. Innate and adaptive immune responses toward nanomedicines. - Iara Maíra de Oliveira Viana;Sabrina Roussel;Joan Defrêne;Eliana Martins Lima;Frédéric Barabé;Nicolas Bertrand - Acta pharmaceutica Sinica. B (2021)
  3. Nanomaterials Synthesis through Microfluidic Methods: An Updated Overview. - Adelina-Gabriela Niculescu;Cristina Chircov;Alexandra Cătălina Bîrcă;Alexandru Mihai Grumezescu - Nanomaterials (Basel, Switzerland) (2021)
  4. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. - Linde Schoenmaker;Dominik Witzigmann;Jayesh A Kulkarni;Rein Verbeke;Gideon Kersten;Wim Jiskoot;Daan J A Crommelin - International journal of pharmaceutics (2021)
  5. 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)
  6. Intracellular Routing and Recognition of Lipid-Based mRNA Nanoparticles. - Christophe Delehedde;Luc Even;Patrick Midoux;Chantal Pichon;Federico Perche - Pharmaceutics (2021)
  7. Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer. - Francesco Mainini;Francesca De Santis;Giovanni Fucà;Massimo Di Nicola;Licia Rivoltini;Michael Eccles - Cancers (2021)
  8. Lipid nanoparticles for mRNA delivery. - Xucheng Hou;Tal Zaks;Robert Langer;Yizhou Dong - Nature reviews. Materials (2021)
  9. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. - Namit Chaudhary;Drew Weissman;Kathryn A Whitehead - Nature reviews. Drug discovery (2021)
  10. Recent Advances and Challenges in Gene Delivery Mediated by Polyester-Based Nanoparticles. - Anna Piperno;Maria Teresa Sciortino;Elena Giusto;Monica Montesi;Silvia Panseri;Angela Scala - International journal of nanomedicine (2021)

... (193 更多 篇文献)


© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研