Synthetic PEGylated glycoproteins and their utility in gene delivery

Chang-po Chen; Ji-seon Kim; Dijie Liu; Garrett R Rettig; Marie A McAnuff; Molly E Martin; Kevin G Rice

doi:10.1021/bc060229p

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Synthetic PEGylated glycoproteins and their utility in gene delivery

Journal article

Open access

Peer reviewed

Synthetic PEGylated glycoproteins and their utility in gene delivery

Chang-po Chen, Ji-seon Kim, Dijie Liu, Garrett R Rettig, Marie A McAnuff, Molly E Martin and Kevin G Rice

Bioconjugate chemistry, Vol.18(2), pp.371-378

03/2007

DOI: 10.1021/bc060229p

PMCID: PMC2653852

PMID: 17373767

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https://www.ncbi.nlm.nih.gov/pmc/articles/2653852View

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Abstract

PEGylated glycoproteins (PGPs) were synthesized by copolymerizing a Cys-terminated PEG-peptide, glycopeptide, and melittin peptide. Compositionally unique PGPs were prepared by varying the ratio of PEG-peptide (20-90%) and melittin (0-70%) with a constant amount of glycopeptide (10%). The PGPs were purified by RP-HPLC, and characterized for molecular weight and polydispersity by GPC-HPLC and SDS-PAGE and for composition by RP-HPLC following reduction to form monomeric peptides. PGPs formed DNA condensates of 200-300 nm in diameter that were administered to mice via the tail vein. Biodistribution studies confirmed their primary targeting to liver hepatocytes with a DNA metabolic half-life of 1 h. Upon stimulation by hydrodynamic dosing with saline, PGP DNA (5 microg) mediated luciferase expression in the liver detected by bioluminescence imaging (BLI) after 24 h. The level of gene expression mediated by PGP DNA was 5000-fold less than direct hydrodynamic dosing of an equivalent amount of DNA and was independent of the mol percent of melittin incorporated into the polymer, but dependent on the presence of galactose on PGP. The results establish the ability to prepare three-component gene delivery polymers that function in vivo. Further design improvements in fusogenic peptides for gene delivery and for the simultaneous use of a nuclear targeting strategy will be necessary to approach levels of expression mediated by the direct hydrodynamic dosing of DNA.

Drug Delivery Systems

Transfection

Gene Targeting

Gene Expression

Plasmids

Luciferases - metabolism

Molecular Weight

Melitten

Glycopeptides - chemistry

Polyethylene Glycols - chemistry

Chromatography, High Pressure Liquid

Glycoproteins - pharmacology

Drug Carriers

Luciferases - genetics

Tissue Distribution

Glycoproteins - chemistry

Glycoproteins - genetics

Gene Transfer Techniques

Liver - metabolism

DNA - administration & dosage

Mice, Inbred ICR

DNA - chemistry

Peptide Fragments - chemistry

Animals

Liver - cytology

Mice

Details

Title: Subtitle: Synthetic PEGylated glycoproteins and their utility in gene delivery
Creators: Chang-po Chen - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA
Ji-seon Kim
Dijie Liu
Garrett R Rettig
Marie A McAnuff
Molly E Martin
Kevin G Rice
Resource Type: Journal article
Publication Details: Bioconjugate chemistry, Vol.18(2), pp.371-378
DOI: 10.1021/bc060229p
PMID: 17373767
PMCID: PMC2653852
NLM abbreviation: Bioconjug Chem
ISSN: 1043-1802
eISSN: 1520-4812
Publisher: United States
Grant note: DK063196 / NIDDK NIH HHS T32 GM067795 / NIGMS NIH HHS R01 DK063196-04 / NIDDK NIH HHS R01 DK063196 / NIDDK NIH HHS R01 GM087653 / NIGMS NIH HHS
Language: English
Date published: 03/2007
Academic Unit: Radiology; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Pharmacy Practice and Science; Medicinal and Natural Products Chemistry
Record Identifier: 9984065325402771

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