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

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dc.contributor.author Hibbitts, Alan
dc.contributor.author O'Connor, Aoife M.
dc.contributor.author McCarthy, Joanna
dc.contributor.author Forde, Éanna B.
dc.contributor.author Hessman, Gary
dc.contributor.author O'Driscoll, Caitriona M.
dc.contributor.author Cryan, Sally-Ann
dc.contributor.author Devocelle, Marc
dc.date.accessioned 2019-11-20T05:48:37Z
dc.date.available 2019-11-20T05:48:37Z
dc.date.issued 2019-06-10
dc.identifier.citation Hibbitts, 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.9b00265 en
dc.identifier.volume 4 en
dc.identifier.issued 6 en
dc.identifier.startpage 10078 en
dc.identifier.endpage 10088 en
dc.identifier.uri http://hdl.handle.net/10468/9139
dc.identifier.doi 10.1021/acsomega.9b00265 en
dc.description.abstract While 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.sponsorship SFI 06/RFP/CHO024/EC07; SFI IvP 13/IA/1840; BioAT program en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher American Chemical Society en
dc.relation.uri https://pubs.acs.org/doi/10.1021/acsomega.9b00265
dc.rights © 2019 American Chemical Society en
dc.rights.uri https://pubs.acs.org/page/policy/authorchoice_termsofuse.html en
dc.subject Transfection efficiency en
dc.subject Gene inhibition en
dc.subject Cell viability en
dc.subject Gene delivery vector (GDV) en
dc.title Poly(ethylene glycol)-Based Peptidomimetic “PEGtide” of Oligo-Arginine allows for efficient siRNA Transfection and gene inhibition en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Caitriona O'Driscoll, School of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: caitriona.odriscoll@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle ACS Omega en
dc.internal.IRISemailaddress caitriona.odriscoll@ucc.ie en
dc.relation.project info: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.identifier.eissn 2470-1343

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