mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications

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

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Strategies to reduce the risks of mRNA drug and vaccine toxicity

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(4), P. 281 - 300

Published: Jan. 23, 2024

Language: Английский

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From structural design to delivery: mRNA therapeutics for cancer immunotherapy

Exploration, Journal Year: 2023, Volume and Issue: 4(2)

Published: Nov. 17, 2023

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority expressing all sequence‐known proteins vivo. In particular, a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens present epitopes to T lymphocytes elicit antitumor effects. addition, receptors like chimeric antigen receptor (CAR), T‐cell (TCR), CD134, immune‐modulating factors including cytokines, interferons, antibodies specific enhance immunological response against tumors. With the maturation vitro transcription (IVT) technology, large‐scale pure encoding be synthesized quickly. However, clinical translation mRNA‐based anticancer strategies is restricted by delivering into target organs or inadequate endosomal escape efficiency mRNA. Recently, there been some advances immunotherapy, which roughly classified modifications structure development delivery systems, especially lipid nanoparticle platforms. this review, latest overcoming limitations immunotherapies recent are summarized. Challenges opportunities applications also discussed.

Language: Английский

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Biomaterials for in situ cell therapy

BMEMat, Journal Year: 2023, Volume and Issue: 1(3)

Published: July 19, 2023

Abstract Cell therapy has revolutionized the treatment of various diseases, such as cancers, genetic disorders, and autoimmune diseases. Currently, most cell products rely on ex vivo engineering, which requires sophisticated manufacturing processes poses safety concerns. The implementation in situ holds potential to overcome current limitations provides a broad range applications clinical feasibility future. A variety biomaterials have been developed improve function target delivery specific types due their excellent biocompatibility, tunable properties, other functionalities, provide reliable method achieve modulation reprogramming. In this article, we summarize recent advances for including T cells, macrophages, dendritic stem cells reprogramming leveraging lipid nanoparticles, polymers, inorganic materials, biomaterials. Finally, discuss challenges future perspectives therapy.

Language: Английский

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Lipid carriers for mRNA delivery

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(10), P. 4105 - 4126

Published: Nov. 30, 2022

Messenger RNA (mRNA) is the template for protein biosynthesis and emerging as an essential active molecule to combat various diseases, including viral infection cancer. Especially, mRNA-based vaccines, a new type of vaccine, have played leading role in fighting against current global pandemic COVID-19. However, inherent drawbacks, large size, negative charge, instability, hinder its use therapeutic agent. Lipid carriers are distinguishable promising vehicles mRNA delivery, owning capacity encapsulate deliver negatively charged drugs targeted tissues release cargoes at desired time. Here, we first summarized structure properties different lipid carriers, such liposomes, liposome-like nanoparticles, solid lipid-polymer hybrid nanoemulsions, exosomes lipoprotein particles, their applications delivering mRNA. Then, development lipid-based formulations vaccine delivery systems was discussed highlighted. Recent advancements COVID-19 were emphasized. Finally, described our future vision perspectives this field.

Language: Английский

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mRNA Cancer Vaccines: Construction and Boosting Strategies

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19550 - 19580

Published: Oct. 11, 2023

In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for prevention of COVID-19, which has pushed this field to be more closely studied motivated researchers delve deeper into therapeutics. To date, research on cancer vaccines been developed rapidly, substantial hopeful therapeutic results have achieved against various solid tumors in clinical trials. review, we first introduce three main components vaccines, including antigens, adjuvants, delivery vectors. Engineering these can optimize effects vaccines. For instance, appropriate modification structure alleviate poor stability innate immunogenicity mRNA, use vectors address issues low efficiency vivo. Second, emphatically discuss some strategies further improve efficacy namely modulating immunosuppressive tumor environment, optimizing administration routes, achieving targeting intended tissues or organs, employing combination therapy. These strengthen inhibitory ability increase possibility elimination. Finally, point out challenges practice offer our perspectives future developments rapidly evolving field. It is anticipated that will therapy near future.

Language: Английский

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Chemically engineering cells for precision medicine

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(3), P. 1068 - 1102

Published: Jan. 1, 2023

This review summarizes chemical tools for cell engineering, introduces their wide application in diagnosis and therapy, discusses the challenges opportunities precision medicine.

Language: Английский

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Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 5, 2023

Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life at protein level cannot meet clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel achieve sustained more efficient and safe regeneration.Bmp2 mRNA was enriched exosomes by selective inhibition translation in donor cells, NoBody (non-annotated P-body dissociating polypeptide, a that inhibits translation) modified plasmids co-transfected. The derived named ExoBMP2+NoBody. vitro experiments confirmed ExoBMP2+NoBody had higher abundance thus stronger osteogenic induction capacity. When GelMA via ally-L-glycine CP05 linker, could be slowly released ensure prolonged effect when endocytosed recipient cells. vivo calvarial defect model, ExoBMP2+NoBody-loaded displayed great capacity promoting regeneration.Together, proposed can provide an innovative strategy regeneration.

Language: Английский

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A preparation method for mRNA-LNPs with improved properties

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 364, P. 632 - 643

Published: Nov. 16, 2023

Language: Английский

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Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

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