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

doi:10.2217/nnm-2021-0180

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 journal › Article › peer-review

5 Citations (Scopus)

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 language	English
Journal	Nanomedicine
Volume	16
Issue number	22
Early online date	26 Aug 2021
DOIs	https://doi.org/10.2217/nnm-2021-0180
Publication status	Published - Sept 2021

Keywords

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

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@article{d06b5967b48344029dbf3056287a49b6,

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

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.",

keywords = "Research Article, FKBPL, gene delivery, preeclampsia, RALA, sFlt-1, trophoblast cells",

author = "Ross McNally and Abdelrahim Alqudah and McErlean, {Emma M} and Claire Rennie and Nabila Morshed and Amy Short and Kristine McGrath and Olga Shimoni and Tracy Robson and McCarthy, {Helen O} and Lana McClements",

year = "2021",

month = sep,

doi = "10.2217/nnm-2021-0180",

language = "English",

volume = "16",

journal = "Nanomedicine",

issn = "1743-5889",

publisher = "Taylor and Francis",

number = "22",

}

TY - JOUR

T1 - Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia

AU - McNally, Ross

AU - Alqudah, Abdelrahim

AU - McErlean, Emma M

AU - Rennie, Claire

AU - Morshed, Nabila

AU - Short, Amy

AU - McGrath, Kristine

AU - Shimoni, Olga

AU - Robson, Tracy

AU - McCarthy, Helen O

AU - McClements, Lana

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - Research Article

KW - FKBPL

KW - gene delivery

KW - preeclampsia

KW - RALA

KW - sFlt-1

KW - trophoblast cells

U2 - 10.2217/nnm-2021-0180

DO - 10.2217/nnm-2021-0180

M3 - Article

SN - 1743-5889

VL - 16

JO - Nanomedicine

JF - Nanomedicine

IS - 22

ER -

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

Abstract

Keywords

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