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Comparison of the expression kinetics and immunostimulatory activity of replicating mRNA, nonreplicating mRNA, and pDNA after intradermal electroporation in pigs

(2018) MOLECULAR PHARMACEUTICS. 15(2). p.377-384
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Abstract
Synthetic mRNA is becoming increasingly popular as an alternative to pDNA-based gene therapy. Currently, multiple synthetic mRNA platforms have been developed. In this study we investigated the expression kinetics and the changes in mRNA encoding cytokine and chemokine levels following intradermal electroporation in pigs of pDNA, self-replicating mRNA., and modified and unmodified mRNA. The self-replicating mRNA tended to induce the highest protein expression, followed by pDNA, modified mRNA, and unmodified mRNA. Interestingly, the self-replicating mRNA. was able to maintain its high expression levels during at least 12 days. In contrast, the expression of pDNA and the nonreplicating inRNAs dropped after respectively one and two days. Six days after intradermal electroporation a dose-dependent expression was observed for all vectors. Again, also at lower doses, the self-replicating mRNA tended to show the highest expression. All the mRNA vectors, including the modified mRNA, induced elevated levels of mRNA encoding cytokines and chemokines in the porcine skin after intradermal electroporation, while no such response was noticed after intradermal electroporation of the pDNA vector.
Keywords
pigs, pDNA, mRNA-therapeutics, luciferase expression, innate immune response, INNATE IMMUNE-RESPONSE, NONVIRAL DELIVERY, GENE-THERAPY, DNA VACCINES, CATIONIC NANOEMULSION, FIREFLY LUCIFERASE, RHESUS MACAQUES, REPORTER GENE, IN-VITRO, VACCINATION

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Chicago
Leyman, Bregje, Hanne Huysmans, Séan Mc Cafferty, Francis Combes, Eric Cox, Bert Devriendt, and Niek Sanders. 2018. “Comparison of the Expression Kinetics and Immunostimulatory Activity of Replicating mRNA, Nonreplicating mRNA, and pDNA After Intradermal Electroporation in Pigs.” Molecular Pharmaceutics 15 (2): 377–384.
APA
Leyman, Bregje, Huysmans, H., Mc Cafferty, S., Combes, F., Cox, E., Devriendt, B., & Sanders, N. (2018). Comparison of the expression kinetics and immunostimulatory activity of replicating mRNA, nonreplicating mRNA, and pDNA after intradermal electroporation in pigs. MOLECULAR PHARMACEUTICS, 15(2), 377–384.
Vancouver
1.
Leyman B, Huysmans H, Mc Cafferty S, Combes F, Cox E, Devriendt B, et al. Comparison of the expression kinetics and immunostimulatory activity of replicating mRNA, nonreplicating mRNA, and pDNA after intradermal electroporation in pigs. MOLECULAR PHARMACEUTICS. 2018;15(2):377–84.
MLA
Leyman, Bregje, Hanne Huysmans, Séan Mc Cafferty, et al. “Comparison of the Expression Kinetics and Immunostimulatory Activity of Replicating mRNA, Nonreplicating mRNA, and pDNA After Intradermal Electroporation in Pigs.” MOLECULAR PHARMACEUTICS 15.2 (2018): 377–384. Print.
@article{8550586,
  abstract     = {Synthetic mRNA is becoming increasingly popular as an alternative to pDNA-based gene therapy. Currently, multiple synthetic mRNA platforms have been developed. In this study we investigated the expression kinetics and the changes in mRNA encoding cytokine and chemokine levels following intradermal electroporation in pigs of pDNA, self-replicating mRNA., and modified and unmodified mRNA. The self-replicating mRNA tended to induce the highest protein expression, followed by pDNA, modified mRNA, and unmodified mRNA. Interestingly, the self-replicating mRNA. was able to maintain its high expression levels during at least 12 days. In contrast, the expression of pDNA and the nonreplicating inRNAs dropped after respectively one and two days. Six days after intradermal electroporation a dose-dependent expression was observed for all vectors. Again, also at lower doses, the self-replicating mRNA tended to show the highest expression. All the mRNA vectors, including the modified mRNA, induced elevated levels of mRNA encoding cytokines and chemokines in the porcine skin after intradermal electroporation, while no such response was noticed after intradermal electroporation of the pDNA vector.},
  author       = {Leyman, Bregje and Huysmans, Hanne and Mc Cafferty, S{\'e}an and Combes, Francis and Cox, Eric and Devriendt, Bert and Sanders, Niek},
  issn         = {1543-8384},
  journal      = {MOLECULAR PHARMACEUTICS},
  language     = {eng},
  number       = {2},
  pages        = {377--384},
  title        = {Comparison of the expression kinetics and immunostimulatory activity of replicating mRNA, nonreplicating mRNA, and pDNA after intradermal electroporation in pigs},
  url          = {http://dx.doi.org/10.1021/acs.molpharmaceut.7b00722},
  volume       = {15},
  year         = {2018},
}

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