title: Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition.
abstract: Green fluorescent protein (GFP) antisense oligodeoxynucleotide (ODN) was covalently conjugated to hyaluronic acid (HA) via a reducible disulfide linkage, and the HA-ODN conjugate was complexed with protamine to increase the extent of cellular uptake and enhance the gene inhibition efficiency of GFP expression. The HA-ODN conjugate formed more stable polyelectrolyte complexes with protamine as compared to naked ODN, probably because of its increased charge density. The higher cellular uptake of protamine/HA-ODN complexes than that of protamine/naked ODN complexes was attributed to the formation of more compact nanosized complexes (approximately 200 nm in diameter) in aqueous solution. Protamine/HA-ODN complexes also showed a comparable level of GFP gene inhibition to that of cytotoxic polyethylenimine (PEI)/ODN complexes. Since both HA and protamine are naturally occurring biocompatible materials, the current formulation based on a cleavable conjugation strategy of ODN to HA could be potentially applied as safe and effective nonviral carriers for ODN and siRNA nucleic acid therapeutics.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Hyejung
authors.initials: H
authors.lastname: Mok
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects* / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D011479:Protamines / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D004220:Disulfides; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D011479:Protamines; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid