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Novel promising PPI and PEI-PPI based polymeric carriers for sa-mRNA vaccines

Lisa Opsomer (UGent)
Author
Organization
Abstract
Recently, mRNA-based vaccines have been introduced worldwide to combat the Covid-19pandemic. These mRNA vaccines are formulated into lipid nanoparticles (LNPs) that protectthe mRNA vaccines against degradation and facilitate their intracellular delivery. Thisadvanced technology has proven its effectiveness, but there is still room for improvement,such as simplification of the formulation. Therefore, we designed a novel polymeric carrierplatform as an alternative to the LNP carrier. Our platform consists of concatenated ethyleneimine and propylene imine monomers, resulting in linear poly(ethylene imine)-poly(propyleneimine)(L-PEI-PPI)polymerswithcontrollabledegreesofpolymerization.Formulation of self-amplifying (sa)-mRNA with these L-PEI-PPI polymers resulted in polymericnanoparticles (PNPs) whose properties depended on the RNA/polymer mixing ratio, i.e. theratio ofnitrogenatoms presentinthepolymersand thephosphategroups ofthe RNAstrands (N/P ratio). Starting from a six-membered polymer library, two polymers showedcomparable and/or superior sa-mRNA transfection efficiencies in different cell lines asopposedto theinvitrogoldstandardcarrierLipofectamineMessengerMax(LFMM).Physicochemical properties such as size, zeta potential, encapsulation efficiency, but alsoprotection against RNase A degradation and toxicity towards diverse cell lines and RBCs weredetermined for the best performing PNPs. These data show that the polymers are able toefficiently condense the sa-mRNA into nanometer-sized particles, which are less toxictowards cells than LFMM, and protect the sa-mRNA form degradation by RNase A. In sum,the discovered PEI-PPI polymers are very efficient sa-mRNA carriers that allow a simple andone-stepformulationofmRNA vaccines.
Keywords
RNA, vaccines, polymers, carrier

Citation

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MLA
Opsomer, Lisa. “Novel Promising PPI and PEI-PPI Based Polymeric Carriers for Sa-MRNA Vaccines.” Research Day 2022, Abstracts, 2022.
APA
Opsomer, L. (2022). Novel promising PPI and PEI-PPI based polymeric carriers for sa-mRNA vaccines. Research Day 2022, Abstracts. Presented at the Research Day 2022, Gent.
Chicago author-date
Opsomer, Lisa. 2022. “Novel Promising PPI and PEI-PPI Based Polymeric Carriers for Sa-MRNA Vaccines.” In Research Day 2022, Abstracts.
Chicago author-date (all authors)
Opsomer, Lisa. 2022. “Novel Promising PPI and PEI-PPI Based Polymeric Carriers for Sa-MRNA Vaccines.” In Research Day 2022, Abstracts.
Vancouver
1.
Opsomer L. Novel promising PPI and PEI-PPI based polymeric carriers for sa-mRNA vaccines. In: Research Day 2022, Abstracts. 2022.
IEEE
[1]
L. Opsomer, “Novel promising PPI and PEI-PPI based polymeric carriers for sa-mRNA vaccines,” in Research Day 2022, Abstracts, Gent, 2022.
@inproceedings{8750050,
  abstract     = {{Recently,  mRNA-based  vaccines  have  been  introduced  worldwide  to  combat  the  Covid-19pandemic.  These  mRNA  vaccines are  formulated  into  lipid  nanoparticles  (LNPs)  that  protectthe  mRNA  vaccines  against  degradation  and  facilitate  their intracellular delivery. Thisadvanced technology has proven its effectiveness, but there is still room for improvement,such as simplification of the formulation. Therefore, we designed a novel polymeric carrierplatform as an alternative to the LNP carrier.   Our   platform   consists   of   concatenated   ethyleneimine  and   propylene  imine  monomers,   resulting   in   linear poly(ethylene imine)-poly(propyleneimine)(L-PEI-PPI)polymerswithcontrollabledegreesofpolymerization.Formulation of  self-amplifying  (sa)-mRNA  with  these  L-PEI-PPI  polymers  resulted  in  polymericnanoparticles  (PNPs)  whose  properties depended  on  the  RNA/polymer  mixing  ratio,  i.e.  theratio  ofnitrogenatoms  presentinthepolymersand  thephosphategroups  ofthe  RNAstrands  (N/P  ratio).  Starting  from  a  six-membered  polymer  library,  two  polymers  showedcomparable and/or  superior  sa-mRNA  transfection  efficiencies  in  different  cell  lines  asopposedto  theinvitrogoldstandardcarrierLipofectamineMessengerMax(LFMM).Physicochemical properties such as size, zeta potential, encapsulation efficiency, but alsoprotection against RNase A degradation and toxicity towards diverse cell lines and RBCs weredetermined for the best performing  PNPs.  These  data  show  that  the  polymers  are  able  toefficiently  condense  the  sa-mRNA  into  nanometer-sized particles, which are less toxictowards cells than LFMM, and protect the sa-mRNA form degradation by RNase A. In sum,the discovered  PEI-PPI  polymers  are  very  efficient  sa-mRNA  carriers  that  allow  a  simple  andone-stepformulationofmRNA vaccines.}},
  author       = {{Opsomer, Lisa}},
  booktitle    = {{Research Day 2022, Abstracts}},
  keywords     = {{RNA,vaccines,polymers,carrier}},
  language     = {{eng}},
  location     = {{Gent}},
  title        = {{Novel promising PPI and PEI-PPI based polymeric carriers for sa-mRNA vaccines}},
  year         = {{2022}},
}