mRNA delivery technologies: Toward clinical translation

Gómez-Aguado, Itziar; Rodríguez-Castejón, Julen; Beraza-Millor, Marina; Rodríguez-Gascón, Alicia; Pozo-Rodríguez, Ana del; Solinís, Maria Ángelés

doi:10.1016/bs.ircmb.2022.04.010

Cited by 11 publications

(9 citation statements)

References 314 publications

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“…As a global pandemic illness, COVID-19 has had a tremendous impact on public health administration in various areas in this world 28,29 , while it has also promoted technical progress in vaccine research and development 30 . mRNA vaccines, a major breakthrough in vaccine history, provided us with a paragon with not only novel vaccine research techniques but also novel ideas for vaccine design and development 31 . This technological creativity resulted in a kind of infectious agent biological mimicry, which actually leads to an organized immune response elicited by the stimulation of the host in an optimized manner that is similar to that during viral infection.…”

Section: Discussionmentioning

confidence: 99%

A new vaccine strategy based on VLSs for use against SARS-CoV-2 variants: Evaluation of their immune effectiveness and investigation of the mechanism

Zhang

et al. 2023

Preprint

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A new lipid system broadening the capacity of antigen carriage, including mRNA and protein, is established, and an assembled virus-like-structure (VLS) encapsulated mRNA of S1 protein from XBB.1 and loaded S1 protein from omicron BA.1 on the surface is identified. This characterized VLS enables to specifically augment mRNA expression in human respiratory epithelial cells and macrophages via its loaded S1 protein on the surface interacting with ACE2 or DC-SIGN molecules of cells. It also archives effective mRNA expression in mouse dendritic cells (DCs) and macrophages via surface S1 protein binding to DC-SIGN molecules followed by the activation of DCs and macrophages in mice. The intensive antibody response against viral variants in Balb/c mice immunized by VLS was observed to be greater than those immunized by mRNA or protein vaccine alone, while ACE+/+ mice and hamsters immunized with VLS were observed to be more effective for restraining viral replication of the Omicron or Wuhan strain challenge. The mechanism of this robust immunity elicited by VLS was found being involved in the integrated effect of diverse signals from activated innate immunity to the adaptive immune system.

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Section: Discussionmentioning

confidence: 99%

A new vaccine strategy based on VLSs for use against SARS-CoV-2 variants: Evaluation of their immune effectiveness and investigation of the mechanism

Zhang

et al. 2023

Preprint

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“…Effective delivery systems are important for the success of RMPs. Due to RNA’s high molecular weight, hydrophilic nature, and negative charge, it poorly diffuses across cellular membranes on its own 2 , 53 , 36 . While single-stranded ASOs can penetrate certain cells through clathrin- or caveolin-dependent endocytic pathways or nonconventional endocytic pathways 37 , double-stranded siRNA requires specialized formulations such as LNPs or conjugation to ligands like N-acetylgalactosamine (GalNAc) for targeted cellular uptake 54 , 55 .…”

Section: Introductionmentioning

confidence: 99%

“…For mRNA therapeutics and vaccines, encapsulation in carrier systems is often required for cell uptake and protection from degradation by ribonucleases 2 , 57 , 53 . These systems use biomaterials 36 , biological methods 58 , and physical methods 59 for RNA delivery.…”

Section: Introductionmentioning

confidence: 99%

“…However, a key challenge with polymers is poor biodegradability, which poses toxicity from accumulation in the cells 60 . LNPs are currently used for larger RNA molecules 36 , as they provide enhanced RNA delivery and minimize degradation 53 . However, further research is required to ensure efficient delivery of liposomes while minimizing degradation in the liver or kidney for therapeutic applications 1 , 53 .…”

Section: Introductionmentioning

confidence: 99%

“…However, their clinical use has many obstacles including potential genomic integration, immunogenicity, packaging size limits, preexisting immunity, limited upscaling, and expensive manufacturing methods 58 , 61 , 62 . VLPs resemble native viruses but lack pathogenicity and are used for delivery because of their biocompatibility, biodegradability, and targeting ability 53 , 36 . Use of ECVs, such as exosomes, for RNA delivery also elicits enhanced cellular uptake, reduced toxicity, and shows no liver accumulation of the RMP 53 .…”

Section: Introductionmentioning

confidence: 99%

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Breaking the mold with RNA—a “RNAissance” of life science

Jones,

Androsavich,

et al. 2024

npj Genom. Med.

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In the past decade, RNA therapeutics have gone from being a promising concept to one of the most exciting frontiers in healthcare and pharmaceuticals. The field is now entering what many call a renaissance or “RNAissance” which is being fueled by advances in genetic engineering and delivery systems to take on more ambitious development efforts. However, this renaissance is occurring at an unprecedented pace, which will require a different way of thinking if the field is to live up to its full potential. Recognizing this need, this article will provide a forward-looking perspective on the field of RNA medical products and the potential long-term innovations and policy shifts enabled by this revolutionary and game-changing technological platform.

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Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems

Beraza-Millor,

Rodríguez-Castejón,

del Pozo-Rodríguez

et al. 2024

BioDrugs

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Background Genetic substrate reduction therapy (gSRT), which involves the use of nucleic acids to downregulate the genes involved in the biosynthesis of storage substances, has been investigated in the treatment of lysosomal storage diseases (LSDs). Objective To analyze the application of gSRT to the treatment of LSDs, identifying the silencing tools and delivery systems used, and the main challenges for its development and clinical translation, highlighting the contribution of nanotechnology to overcome them. Methods A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines was performed. PubMed, Scopus, and Web of Science databases were used for searching terms related to LSDs and gene-silencing strategies and tools. Results Fabry, Gaucher, and Pompe diseases and mucopolysaccharidoses I and III are the only LSDs for which gSRT has been studied, siRNA and lipid nanoparticles being the silencing strategy and the delivery system most frequently employed, respectively. Only in one recently published study was CRISPR/Cas9 applied to treat Fabry disease. Specific tissue targeting, availability of relevant cell and animal LSD models, and the rare disease condition are the main challenges with gSRT for the treatment of these diseases. Out of the 11 studies identified, only two gSRT studies were evaluated in animal models. Conclusions Nucleic acid therapies are expanding the clinical tools and therapies currently available for LSDs. Recent advances in CRISPR/Cas9 technology and the growing impact of nanotechnology are expected to boost the clinical translation of gSRT in the near future, and not only for LSDs. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40259-024-00674-1.

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mRNA delivery technologies: Toward clinical translation

Cited by 11 publications

References 314 publications

A new vaccine strategy based on VLSs for use against SARS-CoV-2 variants: Evaluation of their immune effectiveness and investigation of the mechanism

A new vaccine strategy based on VLSs for use against SARS-CoV-2 variants: Evaluation of their immune effectiveness and investigation of the mechanism

Breaking the mold with RNA—a “RNAissance” of life science

Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems

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