Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency

McGee, Joshua E.; Kirsch, Jack R.; Kenney, Devin; Cerbo, Faith; Chavez, Elizabeth C.; Shih, Ting-Yu; Douam, Florian; Wong, Wilson W.; Grinstaff, Mark W.

doi:10.1038/s41587-024-02306-z

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2024

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Cited by 8 publications

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Advances in the design and delivery of RNA vaccines for infectious diseases

Lokras,

Bobak,

Baghel

et al. 2024

Advanced Drug Delivery Reviews

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Advances in the design and delivery of RNA vaccines for infectious diseases

Lokras,

Bobak,

Baghel

et al. 2024

Advanced Drug Delivery Reviews

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

Shi,

Wang

et al. 2024

Sig Transduct Target Ther

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

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mRNA vaccines for infectious diseases — advances, challenges and opportunities

Pardi,

Krammer

2024

Nat Rev Drug Discov

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Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency

Cited by 8 publications

References 54 publications

Advances in the design and delivery of RNA vaccines for infectious diseases

Advances in the design and delivery of RNA vaccines for infectious diseases

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

mRNA vaccines for infectious diseases — advances, challenges and opportunities

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