Cationic HDL mimetics enhance in vivo delivery of self-replicating mRNA

Wei He, Angela C. Evans, Amy Rasley, Feliza Bourguet, Sandra Peters, Kurt I. Kamrud, Nathaniel Wang, Bolyn Hubby, Martina Felderman, Heather Gouvis, Matthew A. Coleman, Nicholas O. Fischer

Research output: Contribution to journalArticle

Abstract

In vivo delivery of large RNA molecules has significant implications for novel gene therapy, biologics delivery, and vaccine applications. We have developed cationic nanolipoprotein particles (NLPs) to enhance the complexation and delivery of large self-amplifying mRNAs (replicons) in vivo. NLPs are high-density lipoprotein (HDL) mimetics, comprised of a discoidal lipid bilayer stabilized by apolipoproteins that are readily functionalized to provide a versatile delivery platform. Herein, we systematically screened NLP assembly with a wide range of lipidic and apolipoprotein constituents, using biophysical metrics to identify lead candidates for in vivo RNA delivery. NLPs formulated with cationic lipids successfully complexed with RNA replicons encoding luciferase, provided measurable protection from RNase degradation, and promoted replicon in vivo expression. The NLP complexation of the replicon and in vivo transfection efficiency were further enhanced by modulating the type and percentage of cationic lipid, the ratio of cationic NLP to replicon, and by incorporating additive molecules.

Original languageEnglish (US)
Article number102154
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume24
DOIs
StatePublished - Feb 2020
Externally publishedYes

Keywords

  • Cationic
  • HDL
  • in vivo delivery
  • Nanolipoprotein particle
  • NLP
  • Replicon
  • Self-amplifying mRNA

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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  • Cite this

    He, W., Evans, A. C., Rasley, A., Bourguet, F., Peters, S., Kamrud, K. I., Wang, N., Hubby, B., Felderman, M., Gouvis, H., Coleman, M. A., & Fischer, N. O. (2020). Cationic HDL mimetics enhance in vivo delivery of self-replicating mRNA. Nanomedicine: Nanotechnology, Biology, and Medicine, 24, [102154]. https://doi.org/10.1016/j.nano.2020.102154