Poly(ethylene glycol)-Based Peptidomimetic “PEGtide” of Oligo-Arginine allows for efficient siRNA Transfection and gene inhibition

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dc.contributor.authorHibbitts, Alan
dc.contributor.authorO'Connor, Aoife M.
dc.contributor.authorMcCarthy, Joanna
dc.contributor.authorForde, Éanna B.
dc.contributor.authorHessman, Gary
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.authorCryan, Sally-Ann
dc.contributor.authorDevocelle, Marc
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2019-11-20T05:48:37Z
dc.date.available2019-11-20T05:48:37Z
dc.date.issued2019-06-10
dc.description.abstractWhile a wide range of experimental and commercial transfection reagents are currently available, persistent problems remain regarding their suitability for continued development. These include the transfection efficiency for difficult-to-transfect cell types and the risks of decreased cell viability that may arise from any transfection that does occur. Therefore, research is now turning toward alternative molecules that improve the toxicity profile of the gene delivery vector (GDV), while maintaining the transfection efficiency. Among them, cell-penetrating peptides, such as octa-arginine, have shown significant potential as GDVs. Their pharmacokinetic and pharmacodynamic properties can be enhanced through peptidomimetic conversion, whereby a peptide is modified into a synthetic analogue that mimics its structure and/or function, but whose backbone is not solely based on α-amino acids. Using this technology, novel peptidomimetics were developed by co- and postpolymerization functionalization of substituted ethylene oxides, producing poly(ethylene glycol) (PEG)-based peptidomimetics termed “PEGtides”. Specifically, a PEGtide of the poly(α-amino acid) oligo-arginine [poly(glycidylguanidine)] was assessed for its ability to complex and deliver a small interfering ribonucleic acid (siRNA) using a range of cell assays and high-content analysis. PEGtide–siRNA demonstrated significantly increased internalization and gene inhibition over 24 h in Calu-3 pulmonary epithelial cells compared to commercial controls and octa-arginine-treated samples, with no evidence of toxicity. Furthermore, PEGtide–siRNA nanocomplexes can provide significant levels of gene inhibition in “difficult-to-transfect” mouse embryonic hypothalamic (mHypo N41) cells. Overall, the usefulness of this novel PEGtide for gene delivery was clearly demonstrated, establishing it as a promising candidate for continued translational research.en
dc.description.sponsorshipSFI 06/RFP/CHO024/EC07; SFI IvP 13/IA/1840; BioAT programen
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHibbitts, A., O’Connor, A.M., McCarthy, J., Forde, E.B., Hessman, G., O’Driscoll, C.M., Cryan, S.A. and Devocelle, M., 2019. Poly (ethylene glycol)-Based Peptidomimetic “PEGtide” of Oligo-Arginine Allows for Efficient siRNA Transfection and Gene Inhibition. ACS Omega, 4(6), (10pp). DOI:10.1021/acsomega.9b00265en
dc.identifier.doi10.1021/acsomega.9b00265en
dc.identifier.eissn2470-1343
dc.identifier.endpage10088en
dc.identifier.issued6en
dc.identifier.journaltitleACS Omegaen
dc.identifier.startpage10078en
dc.identifier.urihttps://hdl.handle.net/10468/9139
dc.identifier.volume4en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Strategic Research Cluster/07/SRC/B1154/IE/SRC IDDN: Oral and pulmonary delivery of peptides and genes using novel polymeric particulate constructs- establishment of the Irish Drug Delivery Research Network (IDDN)/en
dc.relation.urihttps://pubs.acs.org/doi/10.1021/acsomega.9b00265
dc.rights© 2019 American Chemical Societyen
dc.rights.urihttps://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlen
dc.subjectTransfection efficiencyen
dc.subjectGene inhibitionen
dc.subjectCell viabilityen
dc.subjectGene delivery vector (GDV)en
dc.titlePoly(ethylene glycol)-Based Peptidomimetic “PEGtide” of Oligo-Arginine allows for efficient siRNA Transfection and gene inhibitionen
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