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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Single-Domain Antibodies as Antibody–Drug Conjugates: From Promise to Practice—A Systematic Review

Cancers, Journal Year: 2024, Volume and Issue: 16(15), P. 2681 - 2681

Published: July 27, 2024

Background: Antibody–drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due acquired resistance potential side Objectives: This study focuses on advances in various ADC components improve both the efficacy safety of these agents, includes analysis several novel formats. work assesses whether unique features VHHs—such as small size, enhanced tissue penetration, stability, cost-effectiveness—make them a viable alternative conventional antibodies reviews current status development. Methods: Following PRISMA guidelines, this focused VHHs ADCs, examining advancements prospects from 1 January 2014 30 June 2024. Searches were conducted PubMed, Cochrane Library, ScienceDirect LILACS using specific terms related single-domain antibodies. Retrieved articles rigorously evaluated, excluding duplicates non-qualifying studies. The selected peer-reviewed analyzed quality synthesized highlight advancements, methods, payloads, future directions research. Results: offer significant advantages drug conjugation over smaller size structure, which enhance penetration enable access previously inaccessible epitopes. Their superior solubility, manufacturability facilitate cost-effective production expand range targetable antigens. Additionally, some naturally cross blood–brain barrier or be easily modified favor making promising targeting brain tumors metastases. Although no VHH–drug (nADC nanoADC) are currently clinical arena, preclinical studies have explored methods linkers. Conclusions: While transforming treatment, mechanisms associated toxicities challenge traditional views bioavailability vary with different types. Severe toxicities, often linked compound instability, effects, nonspecific blood cell interactions, need better understanding. Conversely, rapid distribution, clearance could advantageous, potentially toxicity by minimizing prolonged exposure. These attributes make strong candidates next generation enhancing safety.

Language: Английский

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Challenges and opportunities in single-domain antibody-based tumor immunotherapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189284 - 189284

Published: Feb. 1, 2025

Language: Английский

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Nanobodies targeting the tumor microenvironment and their formulation as nanomedicines

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 4, 2025

Among the emerging strategies for cancer theranostics, nanomedicines offer significant promise in advancing both patients' diagnosis and treatment. In combination with nanobodies, can potentially enhance precision efficiency of drug or imaging agent delivery, addressing key limitations current approaches, such as off-target toxicities. The development will be further accelerated by creation smart nanoparticles, their integration immunotherapy. Obviously, success nano-immunotherapy depend on a comprehensive understanding tumor microenvironment, including complex interplay mechanisms that drive cancer-mediated immunosuppression immune escape. Hence, effective therapeutic targeting microenvironment requires modulation cell function, overcoming resistance associated stromal components extracellular matrix, and/or direct elimination cells. Identifying molecules involved progression is, therefore, essential developing therapies diagnostic tools predict patient responses to treatment monitor outcomes. Current are being designed careful consideration factors choice carrier (e.g., biocompatibility, controlled cargo release) moiety. unique properties nanobodies make them an engineering tool target biological high affinity specificity. this review, we focus latest applications various purposes. We also explore main types nanoparticles used immunotherapies, well formulating nanoparticle-nanobody conjugates. Finally, highlight how nanobody-nanoparticle formulations nanomedicines.

Language: Английский

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Research progress on nanobodies in the diagnosis and treatment of natural toxin poisoning

Nano Today, Journal Year: 2025, Volume and Issue: 62, P. 102711 - 102711

Published: March 19, 2025

Language: Английский

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Nanobodies as innovative immune checkpoint modulators: advancing cancer immunotherapy

Medical Oncology, Journal Year: 2024, Volume and Issue: 42(1)

Published: Dec. 24, 2024

Language: Английский

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