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

ACE mRNA (Additional Chimeric Element incorporated IVT mRNA) for Enhancing Protein Expression by Modulating Immunogenicity

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 6, 2024

Abstract The development of in vitro transcribed mRNA (IVT mRNA)‐based therapeutics/vaccines depends on the management IVT immunogenicity. mRNA, which is used for intracellular protein translation, often triggers unwanted immune responses, interfering with expression and leading to reduced therapeutic efficacy. Currently, predominant approach mitigating responses involves incorporation costly chemically modified nucleotides like pseudouridine (Ψ) or N1‐methylpseudouridine (m1Ψ) into raising concerns about expense potential misincorporation amino acids codon sequences. Here, an Additional Chimeric Element incorporated (ACE mRNA), a novel incorporating two segments within single structure, introduced. first segment retains conventional components prepared unmodified nucleotides, while second, comprised RNA/DNA chimeric elements, aims modulate Notably, ACE demonstrates noteworthy reduction immunogenicity concurrently demonstrating enhanced efficiency. are based ability elements restrict retinoic acid‐inducible gene I (RIG‐I) stimulator interferon genes (STING)‐mediated activation. developed shows great modulating without need thereby advancing safety efficacy mRNA‐based therapeutics/vaccines.

Language: Английский