Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia

Ross McNally, Abdelrahim Alqudah, Emma M McErlean, Claire Rennie, Nabila Morshed, Amy Short, Kristine McGrath, Olga Shimoni, Tracy Robson, Helen O McCarthy, Lana McClements*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Overexpression of sFlt-1 or modulation of FKBPL, key antiangiogenic proteins, are important in the pathogenesis of preeclampsia.

Methods: A newly developed nonviral gene-delivery system, RALA, capable of overexpressing sFlt-1 (e15a isoform) was delivered in vivo in transgenic haploinsufficient (Fkbpl+/−) mice. RALA was also used in vitro to deliver human Flt1 (hFlt1) in trophoblast cells.

Results: Serum stable and nontoxic RALA/DNA-based nanoparticles induced an increase in sFlt-1 protein levels in the blood and total protein in the urine; the effect was more pronounced in Fkbpl+/− mice. In vitro, RALA-hFlt nanoparticles significantly reduced secretion of sFlt-1 in trophoblast cells.

Conclusion: The RALA-based genetic nanodelivery system can be safely and effectively applied to emulate preeclampsia-like features or reduce sFlt-1 levels in vitro.
Original languageEnglish
JournalNanomedicine
Volume16
Issue number22
Early online date26 Aug 2021
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Research Article
  • FKBPL
  • gene delivery
  • preeclampsia
  • RALA
  • sFlt-1
  • trophoblast cells

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