Journal article
Synthetic PEGylated glycoproteins and their utility in gene delivery
Bioconjugate chemistry, Vol.18(2), pp.371-378
03/2007
DOI: 10.1021/bc060229p
PMCID: PMC2653852
PMID: 17373767
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.
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, USAJi-seon KimDijie LiuGarrett R RettigMarie A McAnuffMolly E MartinKevin 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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