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Curated Papers > High-impact authoritative literature on "mRNA vaccines"

Self-assembled mRNA vaccines. ​

Literature Information ​

DOI10.1016/j.addr.2020.12.014
PMID33400957
JournalAdvanced drug delivery reviews
Impact Factor17.6
JCR QuartileQ1
Publication Year2021
Times Cited203
KeywordsCOVID-19, Gene delivery, Immunization, Lipid nanoparticles, Self-assembly
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN0169-409X
Pages83-112
Issue170()
AuthorsJeonghwan Kim, Yulia Eygeris, Mohit Gupta, Gaurav Sahay

TL;DR ​

This review explores the evolution of mRNA vaccines, particularly in the context of COVID-19, highlighting advancements in RNA technology, self-assembly of nanoparticles, and key factors influencing mRNA delivery and immune activation. The findings underscore the readiness of mRNA vaccines for clinical use and their potential to revolutionize gene therapy.

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COVID-19 · Gene delivery · Immunization · Lipid nanoparticles · Self-assembly

Abstract ​

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.

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Primary Questions Addressed ​

  1. What are the specific materials used in the self-assembly of mRNA vaccines, and how do their physicochemical properties influence vaccine efficacy?
  2. How does the self-assembly process of mRNA vaccines compare to traditional vaccine development methods in terms of safety and effectiveness?
  3. What challenges are currently faced in the optimization of mRNA sequences for enhanced immune activation in self-assembled vaccines?
  4. In what ways can advancements in nanotechnology further improve the delivery mechanisms of self-assembled mRNA vaccines?
  5. How do the routes of administration for self-assembled mRNA vaccines impact their cellular uptake and overall immunogenic response?

Key Findings ​

Research Background and Objectives ​

The COVID-19 pandemic has accelerated the development of mRNA vaccines, which have transitioned from experimental to front-line therapeutics. This review discusses the design, self-assembly, and delivery mechanisms of mRNA vaccines, emphasizing their potential in combating infectious diseases and their implications for future therapeutic applications.

Main Methods/Materials/Experimental Design ​

The review covers several critical aspects of mRNA vaccine development, focusing on self-assembly processes and delivery systems. The key components include:

  1. mRNA Design: Structurally optimized mRNA, including 5' cap modifications, UTRs, and poly(A) tails, to enhance stability and translation efficiency.
  2. Self-Assembly: Utilization of non-covalent interactions to form lipid nanoparticles (LNPs) that encapsulate mRNA for delivery.
  3. Delivery Mechanisms: Various administration routes (intramuscular, subcutaneous, intranasal) are analyzed for their effects on immune response.
  4. Characterization: The physicochemical properties of mRNA and delivery systems, including size, charge, and surface composition, are discussed in relation to their impact on vaccine efficacy.

The following flowchart illustrates the key steps in mRNA vaccine development:

Mermaid diagram

Key Results and Findings ​

  1. Efficacy: mRNA vaccines have shown over 90% efficacy in clinical trials, particularly the BNT162b2 and mRNA-1273 vaccines.
  2. Safety: Both vaccines have demonstrated a favorable safety profile, with mild to moderate side effects.
  3. Immune Response: Robust T cell and antibody responses were induced, crucial for long-term immunity.

Main Conclusions/Significance/Innovation ​

The review emphasizes the transformative potential of mRNA vaccines in rapid response to pandemics. The self-assembly approach allows for versatile and efficient vaccine delivery systems, which can be tailored for various therapeutic needs. The advancements in mRNA technology not only pave the way for effective vaccines against COVID-19 but also open avenues for future applications in gene therapy and other infectious diseases.

Research Limitations and Future Directions ​

Despite the successes, challenges remain, including:

  • The need for improved storage conditions for mRNA vaccines.
  • Enhancing the stability and delivery efficiency of mRNA formulations.
  • Expanding the application of mRNA technology beyond infectious diseases to include cancer and genetic disorders.

Future research should focus on optimizing delivery systems and exploring new administration routes to enhance vaccine uptake and efficacy. The ongoing exploration of polymer-based systems may also provide alternatives to lipid nanoparticles, potentially addressing current limitations in mRNA vaccine delivery.

References ​

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Literatures Citing This Work ​

  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 more literatures)

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