Document Detail


Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition.
MedLine Citation:
PMID:  17602578     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Hyejung Mok; Ji Won Park; Tae Gwan Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-28
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  18     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:    2007 Sep-Oct
Date Detail:
Created Date:  2007-09-19     Completed Date:  2007-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1483-9     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Biocompatible Materials / chemical synthesis,  pharmacology*
Disulfides / chemistry
Drug Carriers / pharmacology
Gene Silencing / drug effects*,  physiology
Gene Therapy / methods
Green Fluorescent Proteins / chemistry
Hyaluronic Acid / chemistry*
Nanostructures / chemistry*
Oligonucleotides, Antisense / chemistry*
Protamines / chemistry*
RNA, Small Interfering / metabolism
Time Factors
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Disulfides; 0/Drug Carriers; 0/Oligonucleotides, Antisense; 0/Protamines; 0/RNA, Small Interfering; 147336-22-9/Green Fluorescent Proteins; 9004-61-9/Hyaluronic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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