Appearance
Nanomaterial Delivery Systems for mRNA Vaccines.
Literature Information
| DOI | 10.3390/vaccines9010065 |
|---|---|
| PMID | 33478109 |
| Journal | Vaccines |
| Impact Factor | 3.4 |
| JCR Quartile | Q2 |
| Publication Year | 2021 |
| Times Cited | 229 |
| Keywords | SARS-CoV-2, ionizable lipid, lipid nanoparticle, mRNA, vaccine |
| Literature Type | Journal Article, Review |
| ISSN | 2076-393X |
| Issue | 9(1) |
| Authors | Michael D Buschmann, Manuel J Carrasco, Suman Alishetty, Mikell Paige, Mohamad Gabriel Alameh, Drew Weissman |
TL;DR
This review discusses the pivotal role of lipid nanoparticle delivery systems in the effectiveness of mRNA vaccines for SARS-CoV-2, highlighting their dual function in mRNA expression and as adjuvants. The findings emphasize the critical factors influencing lipid nanoparticle performance, underscoring their significance in advancing vaccine technology and response to infectious diseases.
Search for more papers on MaltSci.com
SARS-CoV-2 · ionizable lipid · lipid nanoparticle · mRNA · vaccine
Abstract
The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. We present an overview of mRNA delivery systems and then focus on the lipid nanoparticles used in the current SARS-CoV-2 vaccine clinical trials. The review concludes with an analysis of the determinants of the performance of lipid nanoparticles in mRNA vaccines.
MaltSci.com AI Research Service
Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining
Primary Questions Addressed
- What are the specific properties of lipid nanoparticles that enhance the efficacy of mRNA vaccines?
- How do different nanomaterial delivery systems compare in terms of safety and immunogenicity for mRNA vaccines?
- What advancements in nanomaterial technology could further improve the delivery and stability of mRNA vaccines?
- How do the roles of lipid nanoparticles as adjuvants impact the overall immune response to mRNA vaccines?
- What are the challenges faced in the large-scale production of lipid nanoparticles for mRNA vaccine applications?
Key Findings
Research Background and Objectives
The rapid development of mRNA vaccines during the COVID-19 pandemic has highlighted the importance of effective delivery systems. This review focuses on the advancements in nanomaterial delivery systems, particularly lipid nanoparticles (LNPs), for mRNA vaccines. The primary objective is to provide a comprehensive overview of mRNA delivery systems, with a specific emphasis on LNPs used in SARS-CoV-2 vaccine clinical trials, and to analyze factors that determine their performance.
Main Methods/Materials/Experimental Design
The review discusses various mRNA delivery systems, primarily focusing on lipid nanoparticles, and outlines their production, structure, and mechanisms of action. The technical route is summarized below:
Key components discussed include:
- Lipid Nanoparticles (LNPs): Composed of ionizable lipids, cholesterol, and PEG-lipids, which facilitate mRNA encapsulation and delivery.
- Ionizable Lipids: Their structure and pKa are critical for endosomal escape and effective delivery to the cytoplasm.
- Encapsulation Mechanisms: The process of forming LNPs through microfluidic mixing of lipids and mRNA.
- Immunogenicity and Stability: Addressing the challenges of mRNA degradation and innate immune activation.
Key Results and Findings
- Efficacy of LNPs: LNPs significantly enhance the delivery and expression of mRNA, achieving up to 1000-fold increase in cellular uptake compared to naked mRNA.
- Clinical Trials: The review summarizes various ongoing clinical trials, demonstrating high efficacy rates (over 94%) for mRNA vaccines developed by Pfizer-BioNTech and Moderna.
- Safety and Reactogenicity: Adverse events are noted, with injection site reactions being common, but the overall safety profile remains favorable.
Main Conclusions/Significance/Innovation
The review concludes that lipid nanoparticles represent a transformative technology for mRNA delivery, particularly in vaccine development. Their ability to enhance mRNA stability, facilitate cellular uptake, and modulate immune responses positions them as a crucial component in the future of vaccine and therapeutic development. The innovation lies in the continuous optimization of LNP formulations, which could lead to improved efficacy and safety profiles for mRNA therapeutics.
Research Limitations and Future Directions
- Limitations: The review acknowledges that while LNPs have shown great promise, challenges such as immunogenicity, potential toxicity, and the need for precise dosing remain. The understanding of the long-term effects of mRNA vaccines is still developing.
- Future Directions: Ongoing research should focus on optimizing LNP formulations for specific applications, enhancing targeting capabilities, and exploring alternative delivery routes such as intranasal administration. Additionally, the exploration of self-amplifying mRNA and other novel lipid formulations could further improve the efficacy of mRNA-based therapies.
This structured summary encapsulates the critical aspects of the review on nanomaterial delivery systems for mRNA vaccines, emphasizing the significance of lipid nanoparticles in modern vaccine technology.
References
- An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. - Lisa A Jackson;Evan J Anderson;Nadine G Rouphael;Paul C Roberts;Mamodikoe Makhene;Rhea N Coler;Michele P McCullough;James D Chappell;Mark R Denison;Laura J Stevens;Andrea J Pruijssers;Adrian McDermott;Britta Flach;Nicole A Doria-Rose;Kizzmekia S Corbett;Kaitlyn M Morabito;Sijy O'Dell;Stephen D Schmidt;Phillip A Swanson;Marcelino Padilla;John R Mascola;Kathleen M Neuzil;Hamilton Bennett;Wellington Sun;Etza Peters;Mat Makowski;Jim Albert;Kaitlyn Cross;Wendy Buchanan;Rhonda Pikaart-Tautges;Julie E Ledgerwood;Barney S Graham;John H Beigel; - The New England journal of medicine (2020)
- Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques. - Frank Liang;Gustaf Lindgren;Ang Lin;Elizabeth A Thompson;Sebastian Ols;Josefine Röhss;Shinu John;Kimberly Hassett;Olga Yuzhakov;Kapil Bahl;Luis A Brito;Hugh Salter;Giuseppe Ciaramella;Karin Loré - Molecular therapy : the journal of the American Society of Gene Therapy (2017)
- 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)
- 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)
- Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier. - Oscar A Marcos-Contreras;Colin F Greineder;Raisa Yu Kiseleva;Hamideh Parhiz;Landis R Walsh;Viviana Zuluaga-Ramirez;Jacob W Myerson;Elizabeth D Hood;Carlos H Villa;Istvan Tombacz;Norbert Pardi;Alecia Seliga;Barbara L Mui;Ying K Tam;Patrick M Glassman;Vladimir V Shuvaev;Jia Nong;Jacob S Brenner;Makan Khoshnejad;Tom Madden;Drew Weissmann;Yuri Persidsky;Vladimir R Muzykantov - Proceedings of the National Academy of Sciences of the United States of America (2020)
- Quantitating Endosomal Escape of a Library of Polymers for mRNA Delivery. - Yuhang Jiang;Qiao Lu;Yongheng Wang;Emily Xu;Alison Ho;Priya Singh;Yifei Wang;Zhaozhong Jiang;Fan Yang;Gregory T Tietjen;Peter Cresswell;W Mark Saltzman - Nano letters (2020)
- In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. - I Hoerr;R Obst;H G Rammensee;G Jung - European journal of immunology (2000)
- mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases. - Giulietta Maruggi;Cuiling Zhang;Junwei Li;Jeffrey B Ulmer;Dong Yu - Molecular therapy : the journal of the American Society of Gene Therapy (2019)
- Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. - Katalin Karikó;Hiromi Muramatsu;Frank A Welsh;János Ludwig;Hiroki Kato;Shizuo Akira;Drew Weissman - Molecular therapy : the journal of the American Society of Gene Therapy (2008)
- Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway. - Christina Lorenz;Mariola Fotin-Mleczek;Günter Roth;Christina Becker;Thanh Chau Dam;Wouter P R Verdurmen;Roland Brock;Jochen Probst;Thomas Schlake - RNA biology (2011)
Literatures Citing This Work
- Synthetic Messenger RNA-Based Vaccines: from Scorn to Hype. - Steve Pascolo - Viruses (2021)
- Nanomaterials Synthesis through Microfluidic Methods: An Updated Overview. - Adelina-Gabriela Niculescu;Cristina Chircov;Alexandra Cătălina Bîrcă;Alexandru Mihai Grumezescu - Nanomaterials (Basel, Switzerland) (2021)
- Role of nanotechnology behind the success of mRNA vaccines for COVID-19. - Amit Khurana;Prince Allawadhi;Isha Khurana;Sachin Allwadhi;Ralf Weiskirchen;Anil Kumar Banothu;Deepak Chhabra;Kamaldeep Joshi;Kala Kumar Bharani - Nano today (2021)
- 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)
- mRNA-Based Vaccines. - Frank Kowalzik;Daniel Schreiner;Christian Jensen;Daniel Teschner;Stephan Gehring;Fred Zepp - Vaccines (2021)
- Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape. - Anthony Torres-Ruesta;Rhonda Sin-Ling Chee;Lisa F P Ng - Microorganisms (2021)
- An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times. - Cielo García-Montero;Oscar Fraile-Martínez;Coral Bravo;Diego Torres-Carranza;Lara Sanchez-Trujillo;Ana M Gómez-Lahoz;Luis G Guijarro;Natalio García-Honduvilla;Angel Asúnsolo;Julia Bujan;Jorge Monserrat;Encarnación Serrano;Melchor Álvarez-Mon;Juan A De León-Luis;Miguel A Álvarez-Mon;Miguel A Ortega - Vaccines (2021)
- Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines. - Virginia Aida;Vasilis C Pliasas;Peter J Neasham;J Fletcher North;Kirklin L McWhorter;Sheniqua R Glover;Constantinos S Kyriakis - Frontiers in veterinary science (2021)
- Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines. - Saed Abbasi;Satoshi Uchida - Pharmaceutics (2021)
- mRNA Innovates the Vaccine Field. - Norbert Pardi - Vaccines (2021)
... (219 more literatures)
© 2025 MaltSci - We reshape scientific research with AI technology
