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

McNally, R; Alqudah, A; McErlean, EM; Rennie, C; Morshed, N; Short, A; McGrath, K; Shimoni, O; Robson, T; McCarthy, HO; McClements, L

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

McNally, R Alqudah, A McErlean, EM Rennie, C Morshed, N

Short, A McGrath, K

Shimoni, O

Robson, T McCarthy, HO McClements, L

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Publisher:: FUTURE MEDICINE LTD
Publication Type:: Journal Article
Citation:: Nanomedicine (Lond), 2021, 16, (22), pp. 1999-2012
Issue Date:: 2021-09

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Field	Value	Language
dc.contributor.author	McNally, R
dc.contributor.author	Alqudah, A
dc.contributor.author	McErlean, EM
dc.contributor.author	Rennie, C
dc.contributor.author	Morshed, N https://orcid.org/0000-0001-6398-616X
dc.contributor.author	Short, A
dc.contributor.author	McGrath, K https://orcid.org/0000-0002-6244-3929
dc.contributor.author	Shimoni, O https://orcid.org/0000-0001-8822-1024
dc.contributor.author	Robson, T
dc.contributor.author	McCarthy, HO
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2022-02-15T03:58:22Z
dc.date.available	2022-02-15T03:58:22Z
dc.date.issued	2021-09
dc.identifier.citation	Nanomedicine (Lond), 2021, 16, (22), pp. 1999-2012
dc.identifier.issn	1743-5889
dc.identifier.issn	1748-6963
dc.identifier.uri	http://hdl.handle.net/10453/154528
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	FUTURE MEDICINE LTD
dc.relation.ispartof	Nanomedicine (Lond)
dc.relation.isbasedon	10.2217/nnm-2021-0180
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0306 Physical Chemistry (incl. Structural), 1004 Medical Biotechnology, 1007 Nanotechnology
dc.subject.classification	Nanoscience & Nanotechnology
dc.subject.mesh	Animals
dc.subject.mesh	Female
dc.subject.mesh	Genetic Therapy
dc.subject.mesh	Genetic Vectors
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Nanoparticles
dc.subject.mesh	Placenta
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Pregnancy
dc.subject.mesh	Protein Isoforms
dc.subject.mesh	Trophoblasts
dc.subject.mesh	Vascular Endothelial Growth Factor Receptor-1
dc.subject.mesh	Trophoblasts
dc.subject.mesh	Placenta
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Mice
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Vascular Endothelial Growth Factor Receptor-1
dc.subject.mesh	Protein Isoforms
dc.subject.mesh	Pregnancy
dc.subject.mesh	Genetic Vectors
dc.subject.mesh	Female
dc.subject.mesh	Nanoparticles
dc.subject.mesh	Genetic Therapy
dc.title	Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia.
dc.type	Journal Article
utslib.citation.volume	16
utslib.location.activity	England
utslib.for	0306 Physical Chemistry (incl. Structural)
utslib.for	1004 Medical Biotechnology
utslib.for	1007 Nanotechnology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-02-15T03:58:21Z
pubs.issue	22
pubs.publication-status	Published
pubs.volume	16
utslib.citation.issue	22

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.

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http://hdl.handle.net/10453/154528