Characterization of the ribonuclease activity on the skin surface

Probst, Jochen; Brechtel, Sonja; Scheel, Birgit; Hoerr, Ingmar; Jung, Günther; Rammensee, Hans‐Georg; Pascolo, Steve

doi:10.1186/1479-0556-4-4

Cited by 75 publications

(31 citation statements)

References 42 publications

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“…Another report demonstrated that freeze-dried naked mRNA is stable for at least 10 months under refrigerated conditions 160 . The stability of mRNA products might also be improved by packaging within nanoparticles or by co-formulation with RNase inhibitors 161 . For lipid-encapsulated mRNA, at least 6 months of stability has been observed (Arbutus Biopharma, personal communication), but longer-term storage of such mRNA–lipid complexes in an unfrozen form has not yet been reported.…”

Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

3,300

3,330

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mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.

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Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

mRNA vaccines — a new era in vaccinology

Pardi

Hogan

Porter

et al. 2018

Nat Rev Drug Discov

3,300

3,330

View full text Add to dashboard Cite

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“…84 Thus, the efficacy of mRNA vaccines may benefit significantly from complexing agents which protect RNA from degradation. Complexation may also enhance uptake by cells and/or improve delivery to the translation machinery in the cytoplasm.…”

Section: Formulation Of Mrnamentioning

confidence: 99%

Developing mRNA-vaccine technologies

et al. 2012

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mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addition, mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the production process, mRNA vaccines also offer maximum flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technology.

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“…It has been shown that local injection of naked mRNA could lead to a specific immune response (10–12). However, this strategy did not lead to high levels of protein expression, as naked mRNA molecules are immediately degraded by tissue nucleases (13). Since the negatively charged mRNA molecules cannot enter antigen-presenting cells directly, mRNA-based vaccine is usually prepared by transfecting mRNA molecules into patient-derived dendritic cells (DCs) by electroporation (14, 15).…”

Section: Introductionmentioning

confidence: 99%

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

et al. 2017

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mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.

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Characterization of the ribonuclease activity on the skin surface

Cited by 75 publications

References 42 publications

mRNA vaccines — a new era in vaccinology

mRNA vaccines — a new era in vaccinology

Developing mRNA-vaccine technologies

Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination

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