mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications DOI Creative Commons
Yu‐Shiuan Wang,

Monika Kumari,

Guanhong Chen

et al.

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Oct. 7, 2023

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating immune system. With regard mRNA vaccines, researchers modified structure enhance its stability promote systemic tolerance of antigenic presentation non-inflammatory contexts. Still, delivery naked mRNAs is inefficient results low levels antigen protein production. As such, lipid nanoparticles been utilized improve protect cargo from extracellular degradation. This advance was milestone development vaccines dispelled skepticism about technology yield clinically approved medicines. Following resounding success COVID-19, many other proposed treatment variety diseases. review begins discussion modifications vehicles, well factors that influence administration routes. Then, we summarize applications discuss further key points pertaining preclinical targeting wide range Finally, latest market trends future drugs.

Language: Английский

Lipid nanoparticles for mRNA delivery DOI Open Access
Xucheng Hou,

Tal Zaks,

Róbert Langer

et al.

Nature Reviews Materials, Journal Year: 2021, Volume and Issue: 6(12), P. 1078 - 1094

Published: Aug. 10, 2021

Language: Английский

Citations

2249
Drug delivery systems for RNA therapeutics DOI Open Access
Kalina Paunovska, David Loughrey, James E. Dahlman

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(5), P. 265 - 280

Published: Jan. 4, 2022

Language: Английский

Citations

832
Lipids and Lipid Derivatives for RNA Delivery DOI
Yuebao Zhang, Changzhen Sun, Chang Wang

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(20), P. 12181 - 12277

Published: July 19, 2021

RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown pathological genes, expression therapeutic proteins, and programmed gene editing. Due to the inherent instability negative-charges RNA molecules, can make most use delivery systems overcome biological barriers release payload into cytosol. Among different types systems, lipid-based particularly lipid nanoparticles (LNPs), been extensively studied due their unique properties, such as simple chemical synthesis components, scalable manufacturing processes LNPs, wide packaging capability. LNPs represent widely used for therapeutics, evidenced by clinical approvals three LNP-RNA formulations, patisiran, BNT162b2, mRNA-1273. This review covers recent advances lipids, derivatives, lipid-derived macromolecules over past several decades. We focus mainly on structures, synthetic routes, characterization, formulation methods, structure–activity relationships. also briefly describe current status representative preclinical studies trials highlight future opportunities challenges.

Language: Английский

Citations

403
An ionizable lipid toolbox for RNA delivery DOI Creative Commons
Xuexiang Han, Hanwen Zhang, Kamila Butowska

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Dec. 13, 2021

Recent years have witnessed incredible growth in RNA therapeutics, which has benefited significantly from decades of research on lipid nanoparticles, specifically its key component—the ionizable lipid. This comment discusses the major types, and provides perspectives for future development. therapeutics

Language: Английский

Citations

369
CRISPR/Cas9 therapeutics: progress and prospects DOI Creative Commons
Tianxiang Li, Yanyan Yang, Hongzhao Qi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 16, 2023

Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety efficient Cas9 variants derivatives have been developed to cope complex genomic changes that occur during diseases. However, strategies effectively deliver CRISPR system diseased cells in vivo are currently lacking, nonviral vectors target recognition functions may be focus research. Pathological physiological resulting from disease onset expected serve as identifying factors targeted delivery targets gene editing. Diseases both varied complex, choice appropriate methods different important. Meanwhile, there still many potential challenges identified when targeting CRISPR/Cas9 treatment. This paper reviews current developments three aspects, namely, type, vector, characteristics. Additionally, this summarizes successful examples clinical trials finally describes possible problems associated applications.

Language: Английский

Citations

321
Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis DOI Creative Commons
Min Qiu, Yan Tang, Jinjin Chen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(8)

Published: Feb. 16, 2022

Significance The current application of messenger RNA (mRNA)-based technology has largely been confined to liver diseases because the lack a specific and efficient extrahepatic in vivo systemic mRNA delivery system. Here, we have developed library N-series lipid nanoparticles (LNPs) that could specifically regulate protein composition corona on surface LNPs, which allows lung. We further demonstrated our lung-targeting LNP effectively deliver mouse tuberous sclerosis complex 2 ( Tsc2 ) into TSC2-null cells restore its function, resulting enhanced control tumor burden preclinical model lymphangioleiomyomatosis, destructive lung disease caused by loss-of-function mutations gene.

Language: Английский

Citations

320
Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs DOI Open Access
Sean A. Dilliard, Daniel J. Siegwart

Nature Reviews Materials, Journal Year: 2023, Volume and Issue: 8(4), P. 282 - 300

Published: Jan. 19, 2023

Language: Английский

Citations

311
Therapeutic in vivo delivery of gene editing agents DOI Creative Commons
Aditya Raguram, Samagya Banskota, David R. Liu

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2806 - 2827

Published: July 1, 2022

In vivo gene editing therapies offer the potential to treat root causes of many genetic diseases. Realizing promise therapeutic in requires ability safely and efficiently deliver agents relevant organs tissues vivo. Here, we review current delivery technologies that have been used enable editing, including viral vectors, lipid nanoparticles, virus-like particles. Since no single modality is likely be appropriate for every possible application, compare benefits drawbacks each method highlight opportunities future improvements.

Language: Английский

Citations

297
Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery DOI Open Access
Xu Wang, Shuai Liu, Yehui Sun

et al.

Nature Protocols, Journal Year: 2022, Volume and Issue: 18(1), P. 265 - 291

Published: Oct. 31, 2022

Language: Английский

Citations

254
Lipid nanoparticle-mediated lymph node–targeting delivery of mRNA cancer vaccine elicits robust CD8 + T cell response DOI Creative Commons
Jinjin Chen, Zhongfeng Ye,

Changfeng Huang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(34)

Published: Aug. 15, 2022

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications mRNA technology. For vaccines, the lymph node (LN) is predicted reduce side effects and increase immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without modification any active targeting ligands developing cancer vaccine. LNP named 113-O12B showed increased specific expression LN compared with formulated ALC-0315, synthetic used COVID-19 vaccine Comirnaty. CD8 + T cell response encoded full-length ovalbumin (OVA) model antigen. As result, protective therapeutic effect OVA-encoding on OVA-antigen–bearing B16F10 melanoma was also improved. Moreover, encapsulated TRP-2 peptide (TRP2 180–188 )–encoding exhibited excellent tumor inhibition, complete 40% regular when combined anti–programmed death-1 (PD-1) therapy, revealing broad application from protein antigens. All treated mice long-term memory, hindering occurrence metastatic nodules lung rechallenging experiments that followed. enhanced antitumor efficacy system shows potential as universal platform next generation vaccines.

Language: Английский

Citations

250