Lipid nanoparticles driving mRNA vaccine innovations: From concept to clinic
Source abstract
Abstract
Messenger RNA (mRNA) vaccines have emerged as a transformative approach to immunization, driven by their ability to encode specific proteins that elicit targeted immune responses. However, the inherent instability of mRNA and its vulnerability to enzymatic degradation have necessitated the development of sophisticated delivery systems. This review explores the latest advancements in non-viral nanoparticle platforms-particularly lipid nanoparticles (LNPs), cationic liposomes, and lipid-polymer hybrids-for the efficient and safe delivery of mRNA. We analyze the structural and functional components of these nanoplatforms such as ionizable lipids, phospholipids, and PEGylated lipids, which enhance mRNA stability, circulation, and cellular uptake. Key challenges, including immunogenicity, cytotoxicity, and the "PEG dilemma" are examined alongside emerging solutions such as stimuli-responsive elements and targeted ligand modifications. Special emphasis is placed on microfluidic synthesis as a scalable production technique for generating uniform, clinically viable mRNA-loaded nanoparticles. By integrating insights from nanotechnology, immunology, and clinical medicine, this review highlights the critical innovations and ongoing challenges that shape the future of mRNA vaccine development. The conclusions drawn underscore the pivotal role of nanoparticle-based delivery systems in maximizing mRNA vaccine efficacy and advancing personalized immunization strategies against infectious diseases and cancer.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: RNA Interference and Gene Delivery · Immunotherapy and Immune Responses · Bacteriophages and microbial interactions
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Recent advancements in mRNA vaccines: from target selection to delivery systems10.3390/vaccines12080873 ↗
2. A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections10.1016/j.ymthe.2024.02.011 ↗
3. SARS-CoV-2 variant-specific mRNA vaccine: pros and cons
4. In vitro transcribed RNA-based platform vaccines: past, present, and future10.3390/vaccines11101600 ↗
5. Advancements of in vitro transcribed mRNA (IVT mRNA) to enable translation into the clinics10.1016/j.addr.2023.114961 ↗
6. Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity10.1016/j.ymthe.2024.03.022 ↗
7. Prospects and challenges in developing mRNA vaccines for infectious diseases and oncogenic viruses
8. Oligonucleotide aptamers: potential novel molecules against viral hepatitis10.4103/1735-5362.202447 ↗
9. Crosstalk of transcriptional regulators of adaptive immune system and microRNAs: an insight into differentiation and development10.3390/cells12040635 ↗
10. Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design10.3389/fimmu.2023.1294929 ↗
11. Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers10.1038/s41551-024-01208-4 ↗
12. Research advances on the stability of mRNA vaccines10.3390/v15030668 ↗
13. Challenges of storage and stability of mRNA-based COVID-19 vaccines10.3390/vaccines9091033 ↗
14. Lipid nanoparticle-based mRNA vaccines: a new frontier in precision oncology10.1093/pcmedi/pbae017 ↗
15. Lipid nanoparticles- from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement10.1021/acsnano.1c04996 ↗
16. Swelling, rupture and endosomal escape of biological nanoparticles per Se and those fused with liposomes in acidic environment10.3390/pharmaceutics16050667 ↗
17. Breaking the final barrier: evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome10.1016/j.addr.2024.115446 ↗
18. mRNA COVID-19 vaccines-facts and hypotheses on fragmentation and encapsulation10.3390/vaccines11010040 ↗
19. An insight overview on COVID-19 mRNA vaccines: advantageous, pharmacology, mechanism of action, and prospective considerations10.1016/j.intimp.2023.109934 ↗
20. Ionizable lipid nanoparticles for mRNA delivery10.1002/anbr.202300006 ↗
21. pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function10.1073/pnas.2310491120 ↗
22. pH-dependent behavior of ionizable cationic lipids in mRNA-carrying lipoplexes investigated by Molecular dynamics simulations10.1002/marc.202100683 ↗
23. The role of lipid components in lipid nanoparticles for vaccines and gene therapy10.1016/j.addr.2022.114416 ↗
24. Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity10.1038/ncomms5277 ↗
25. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo10.1002/anie.201203263 ↗
26. Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs10.1016/j.dmpk.2021.100424 ↗
27. The importance of apparent pKa in the development of nanoparticles encapsulating siRNA and mRNA10.1016/j.tips.2021.03.002 ↗
28. Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond10.52601/bpr.2023.230022 ↗
29. Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia10.1126/sciadv.abm1418 ↗
30. Impact of lipid tail length on the organ selectivity of mRNA-lipid nanoparticles
31. Ionizable lipid nanoparticles encapsulating barcoded mRNA for accelerated in vivo delivery screening10.1016/j.jconrel.2019.10.028 ↗
32. Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery10.1038/s41596-022-00755-x ↗
33. Combinatorial design of ionizable lipid nanoparticles for muscle-selective mRNA delivery with minimized off-target effects10.1073/pnas.2309472120 ↗
34. Ionizable lipid nanoparticle-mediated mRNA delivery for Human CAR T cell engineering10.1021/acs.nanolett.9b04246 ↗
35. Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics10.1016/j.dmpk.2022.100450 ↗
36. Structure and function of cationic and ionizable lipids for nucleic acid delivery10.1007/s11095-022-03460-2 ↗
37. Lipid nanoparticle technologies for nucleic acid delivery: a nanoarchitectonics perspective10.1002/adfm.202203669 ↗
38. Evaluating how cationic lipid affects mRNA-LNP physical properties and biodistribution10.1016/j.ejpb.2023.08.002 ↗
39. PEGylated lipid nanoparticle formulations: immunological safety and efficiency perspective10.1021/acs.bioconjchem.3c00174 ↗
40. Effect of PEG anchor and serum on lipid nanoparticles: development of a nanoparticles tracking method10.3390/pharmaceutics15020597 ↗
41. PEG-peptide inhibition of scavenger receptor uptake of nanoparticles by the liver10.1021/acs.molpharmaceut.8b00355 ↗
42. Anti-PEG antibodies compromise the integrity of PEGylated lipid-based nanoparticles via complement10.1016/j.jconrel.2021.11.042 ↗
43. Effects of PEG antibodies on in vivo performance of LNP-mRNA vaccines10.1016/j.ijpharm.2023.123695 ↗
44. Computational insights into the role of cholesterol in inverted hexagonal phase stabilization and endosomal drug release10.1021/acs.langmuir.2c00430 ↗
45. Effect of cholesterol content of lipid composition in mRNA-LNPs on the protein expression in the injected site and liver after local administration in mice10.1016/j.xphs.2022.12.026 ↗
46. Impact of non-ionizable lipids and phase mixing methods on structural properties of lipid nanoparticle formulations10.1016/j.ijpharm.2023.122874 ↗
47. Lipid nanoparticles for mRNA delivery10.1038/s41578-021-00358-0 ↗
48. Microfluidic technologies and devices for lipid nanoparticle-based RNA delivery10.1016/j.jconrel.2022.02.017 ↗
49. Difference in the lipid nanoparticle technology employed in three approved siRNA (Patisiran) and mRNA (COVID-19 vaccine) drugs10.1016/j.dmpk.2021.100424 ↗
50. mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability10.1016/j.ijpharm.2021.120586 ↗
51. Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines10.1073/pnas.2303567120 ↗
52. High-throughput In vivo screening identifies differential influences on mRNA lipid nanoparticle immune cell delivery by administration route10.1021/acsnano.4c01171 ↗
53. Low-dose mildronate-derived lipidoids for efficient mRNA vaccine delivery with minimal inflammation side effects10.1021/acsnano.4c06160 ↗
54. Discovery of ketal-ester ionizable lipid nanoparticle with reduced hepatotoxicity, enhanced spleen tropism for mRNA vaccine delivery10.1002/advs.202404684 ↗
55. Duration of SARS-CoV-2 mRNA vaccine persistence and factors associated with cardiac involvement in recently vaccinated patients10.1038/s41541-023-00742-7 ↗
56. Potential health risks of mRNA-based vaccine therapy: a hypothesis10.1016/j.mehy.2023.111015 ↗
57. Adenoviral vector DNA-and SARS-CoV-2 mRNA-based Covid-19 vaccines: possible integration into the human genome-are adenoviral genes expressed in vector-based vaccines?10.1016/j.virusres.2021.198466 ↗
58. mRNA: vaccine or gene therapy? The safety regulatory issues10.3390/ijms241310514 ↗
59. The mRNA-LNP vaccines–the good, the bad and the ugly?10.3389/fimmu.2024.1336906 ↗
60. mRNA vaccine quality analysis using RNA sequencing10.1038/s41467-023-41354-y ↗
61. Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics10.1038/s12276-023-01086-x ↗
62. Pro-inflammatory concerns with lipid nanoparticles10.1016/j.ymthe.2022.04.011 ↗
63. Liposomes as adjuvants and vaccine delivery systems10.1134/S1990747822020076 ↗
64. Cationic nanoliposomes meet mRNA: efficient delivery of modified mRNA using hemocompatible and stable vectors for therapeutic applications10.1016/j.omtn.2017.07.013 ↗
65. GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells10.1016/j.jsps.2023.05.017 ↗
66. Exploration of mRNA nanoparticles based on DOTAP through optimization of the helper lipids10.1002/biot.202300123 ↗
67. Efficient mRNA delivery with mRNA lipoplexes prepared using a modified ethanol injection method10.3390/pharmaceutics15041141 ↗
68. Monitoring translation activity of mRNA-loaded nanoparticles in mice10.1021/acs.molpharmaceut.8b00370 ↗
69. Elucidating the encapsulation of short interfering RNA in PEGylated cationic liposomes10.1021/la803973p ↗
70. Nanoparticle delivery systems for DNA/RNA and their potential applications in nanomedicine10.2174/1568026619666191024170212 ↗
71. Optimization of DOTAP/chol cationic lipid nanoparticles for mRNA, pDNA, and oligonucleotide delivery10.1208/s12249-022-02294-w ↗
72. Chemistry of lipid nanoparticles for RNA delivery10.1021/acs.accounts.1c00544 ↗
73. Synthesis of cationic liposome nanoparticles using a thin film dispersed hydration and extrusion method10.1371/journal.pone.0300467 ↗
74. Cationic liposomes produced via ethanol injection method for dendritic cell therapy10.1080/08982104.2016.1196702 ↗
75. Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis10.1080/08982104.2019.1593449 ↗
76. Elucidating structural configuration of lipid assemblies for mRNA delivery systems10.1021/acsnano.4c00587 ↗
77. An overview of lipid constituents in lipid nanoparticle mRNA delivery systems
78. Cationic nanoliposomes meet mRNA: efficient delivery of modified mRNA using hemocompatible and stable vectors for therapeutic applications10.1016/j.omtn.2017.07.013 ↗
79. DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine10.1016/j.jconrel.2020.08.023 ↗
80. Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity10.1016/j.cellimm.2020.104143 ↗
81. Investigating the fate of MP1000-LPX In Vivo by adding serum to transfection medium10.2174/2211738508666200907105224 ↗
82. A review of different types of liposomes and their advancements as a form of gene therapy treatment for breast cancer10.3390/molecules28031498 ↗
83. Biodistribution of rhodamine B fluorescence-labeled cationic nanoparticles in rats10.1007/s11051-013-2221-1 ↗
84. PEGylation of lipoplexes: the right balance between cytotoxicity and siRNA effectiveness10.1016/j.ejps.2016.08.058 ↗
85. Recent advances in the lipid nanoparticle-mediated delivery of mRNA vaccines10.3390/vaccines11030658 ↗
86. Cationic polymers as transfection reagents for nucleic acid delivery10.3390/pharmaceutics15051502 ↗
87. Polymer-based nanomaterials and applications for vaccines and drugs10.3390/polym10010031 ↗
88. Polymeric nonviral gene delivery systems for cancer immunotherapy
89. Glutathione targeted tragacanthic acid-chitosan as a non-viral vector for brain delivery of miRNA-219a-5P: an in vitro/in vivo study10.1016/j.ijbiomac.2022.01.100 ↗
90. A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity10.1038/s41392-021-00634-z ↗
91. Evaluation of mRNA lipoplexes prepared using modified ethanol injection method as a tumour vaccine10.1080/1061186X.2024.2384074 ↗
92. An inoculation site-retained mRNA vaccine induces robust immune responses against SARS-CoV-2 variants10.1016/j.jconrel.2024.01.002 ↗
93. Lipid–polymer hybrid nanoparticle-mediated therapeutics delivery: advances and challenges10.1016/j.drudis.2017.05.015 ↗
94. Robust and long-lasting immunity and protection in mice induced by lipopolyplex-delivered mRNA vaccines expressing the prefusion protein of respiratory syncytial virus10.3390/vaccines13010093 ↗
95. Design and biological activity of novel stealth polymeric lipid nanoparticles for enhanced delivery of hydrophobic photodynamic therapy drugs10.1016/j.nano.2018.07.006 ↗
96. Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial10.1016/j.ebiom.2023.104586 ↗
97. Novel bionic inspired nanosystem construction for precise delivery of mRNA
98. Phase-controlled field-effect micromixing using AC electroosmosis10.1038/s41378-020-0166-y ↗
99. Microfluidic mixing and devices for preparing nanoparticulate drug delivery systems
100. Use of microfluidics to prepare lipid-based nanocarriers10.3390/pharmaceutics15041053 ↗