In vivo delivery of functional Flightless I siRNA using layer-by-layer polymer surface modification

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dc.contributor.authorMartens, P.
dc.contributor.authorLy, M.
dc.contributor.authorAdams, D.
dc.contributor.authorPenzkover, K.
dc.contributor.authorStrudwick, X.
dc.contributor.authorCowin, A.
dc.contributor.authorPoole-Warren, L.
dc.date.issued2015
dc.description.abstractGene silencing using small interfering RNA has been proposed as a therapy for cancer, viral infections and other diseases. This study aimed to investigate whether layer-by-layer polymer surface modification could deliver small interfering RNA to decrease fibrotic processes associated with medical device implantation. Anti-green fluorescent protein labelled small interfering RNA was applied to tissue culture plates and polyurethane using a layer-by-layer technique with small interfering RNA and poly-L-lysine. In vitro studies showed that the level of down-regulation of green fluorescent protein was directly related to the number of coatings applied. This layer-by-layer coating technique was then used to generate Rhodamine-Flii small interfering RNA-coated implants for in vivo studies of small interfering RNA delivery via subcutaneous implantation in mice. After two days, Rh-positive cells were observed on the implants' surface indicating cellular uptake of the Rhodamine-Flii small interfering RNA. Decreased Flii gene expression was observed in tissue surrounding the Rhodamine-Flii small interfering RNA coated implants for up to seven days post implantation, returning to baseline by day 21. Genes downstream from Flii, including TGF-β1 and TGF-β3, showed significantly altered expression confirming a functional effect of the Rhodamine-Flii small interfering RNA on gene expression. This research demonstrates proof-of-principle that small interfering RNA can be delivered via layer-by-layer coatings on biomaterials and thereby can alter the fibrotic process.
dc.description.statementofresponsibilityPenny J Martens, Mai Ly, Damian H Adams, Kathryn R Penzkover, Xanthe Strudwick, Allison J Cowin, and Laura A Poole-Warren
dc.identifier.citationJournal of Biomaterials Applications, 2015; 30(3):257-268
dc.identifier.doi10.1177/0885328215579422
dc.identifier.issn0885-3282
dc.identifier.issn1530-8022
dc.identifier.orcidCowin, A. [0000-0003-2885-2080]
dc.identifier.urihttp://hdl.handle.net/2440/109906
dc.language.isoen
dc.publisherSAGE Publications
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002009
dc.rights© The Author(s) 2015
dc.source.urihttps://doi.org/10.1177/0885328215579422
dc.subjectAnimal model; drug delivery; polyurethane; siRNA
dc.titleIn vivo delivery of functional Flightless I siRNA using layer-by-layer polymer surface modification
dc.typeJournal article
pubs.publication-statusPublished

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