An Update on Self-Amplifying mRNA Vaccine Development

Blakney, Anna K.; Ip, Shell; Geall, Andrew J.

doi:10.3390/vaccines9020097

Cited by 158 publications

(169 citation statements)

References 165 publications

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“…Over multiple years, both immunotherapy and non-immunotherapy mRNA therapeutic fields underwent a great deal of innovation and significant growth. Self-amplifying mRNA (saRNA) encode replicase and protein of interest and replicate in cells utilizing viral replication strategy (comprehensively reviewed elsewhere [ 164 , 165 ]). saRNA generate dsRNA intermediate during their cellular amplification, are potent activators of the immune system, and are one of the innovative tools in immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety

Vlatkovic

2021

Biomedicines

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Lipid nanoparticle (LNP) formulated messenger RNA-based (LNP-mRNA) vaccines came into the spotlight as the first vaccines against SARS-CoV-2 virus to be applied worldwide. Long-known benefits of mRNA-based technologies consisting of relatively simple and fast engineering of mRNA encoding for antigens and proteins of interest, no genomic integration, and fast and efficient manufacturing process compared with other biologics have been verified, thus establishing a basis for a broad range of applications. The intrinsic immunogenicity of LNP formulated in vitro transcribed (IVT) mRNA is beneficial to the LNP-mRNA vaccines. However, avoiding immune activation is critical for therapeutic applications of LNP-mRNA for protein replacement where targeted mRNA expression and repetitive administration of high doses for a lifetime are required. This review summarizes our current understanding of immune activation induced by mRNA, IVT byproducts, and LNP. It gives a comprehensive overview of the present status of preclinical and clinical studies in which LNP-mRNA is used for protein replacement and treatment of rare diseases with an emphasis on safety. Moreover, the review outlines innovations and strategies to advance pharmacology and safety of LNP-mRNA for non-immunotherapy applications.

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Section: Discussionmentioning

confidence: 99%

Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety

Vlatkovic

2021

Biomedicines

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“…SARS‐CoV‐2 was associated with an outbreak of atypical pneumonia, named COronaVIrus Disease 2019 (COVID‐19), that rapidly spread from China to all continents, unleashing a global infection. [ 339 , 340 ] Coronaviruses consist of a positive‐sense, non‐segmented, single‐stranded mRNA [(+)ssRNA] of ≈30 Kb, enveloped in a helical nucleocapsid. The viral RNA encodes a set of 28 specific proteins grouped into three main categories: i) non‐structural proteins (Nsp1 to Nsp16); ii) structural spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins; and iii) the accessory proteins (orf3a, orf6, orf7a, orf7b, orf8, orf9b, orf9c, and orf10).…”

Section: Rna Delivery Applicationsmentioning

confidence: 99%

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

et al. 2021

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In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA‐based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology‐assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in‐depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology‐mediated RNA therapies are discussed.

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“…The development of mRNA-based vaccines against infectious diseases has been previously summarized in self amplifying and conventional non-replicating RNA technologies [112,124,125]. This section reviews recent updates on preclinical and clinical studies on mRNA vaccines against other viruses, including human respiratory syncytial virus (RSV), Zika virus, rabies, and human immunodeficiency virus (HIV).…”

Section: Other Viral Mrna Vaccinesmentioning

confidence: 99%

An Update on mRNA-Based Viral Vaccines

et al. 2021

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With the success of COVID-19 vaccines, newly created mRNA vaccines against other infectious diseases are beginning to emerge. Here, we review the structural elements required for designing mRNA vaccine constructs for effective in vitro synthetic transcription reactions. The unprecedently speedy development of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was enabled with previous innovations in nucleoside modifications during in vitro transcription and lipid nanoparticle delivery materials of mRNA. Recent updates are briefly described in the status of mRNA vaccines against SARS-CoV-2, influenza virus, and other viral pathogens. Unique features of mRNA vaccine platforms and future perspectives are discussed.

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An Update on Self-Amplifying mRNA Vaccine Development

Cited by 158 publications

References 165 publications

Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety

Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety

Nanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines

An Update on mRNA-Based Viral Vaccines

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