Synthetic PEGylated glycoproteins and their utility in gene delivery.

Synthetic PEGylated glycoproteins and their utility in gene delivery. Research Abstract Details 

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Synthetic PEGylated glycoproteins and their utility in gene delivery. Abstract Text:

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

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.

Synthetic PEGylated glycoproteins and their utility in gene delivery. Publishing Authors By Initials

CP Chen,JS Kim,D Liu,GR Rettig,MA McAnuff,ME Martin,KG Rice,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Synthetic PEGylated glycoproteins and their utility in gene delivery. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Bioconjugate chemistry

VOLUME: 18

Page Numbers: 371-8

Journal Abbreviation: Bioconjug. Chem.

ISSN: 1043-1802

DAY: 3

MONTH: 12

YEAR: 2007

Synthetic PEGylated glycoproteins and their utility in gene delivery. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9010319

Synthetic PEGylated glycoproteins and their utility in gene delivery. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: chemistry

Chemical & Substance for Abstract: Synthetic PEGylated glycoproteins and their utility in gene delivery. Information

Substance Name: Luciferases

Registry Number: EC 1.13.12.-

Grant and Affiliation Information for Synthetic PEGylated glycoproteins and their utility in gene delivery.

AFFILIATION: Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK063196

ACRONYM: DK

MEDLINETA: Bioconjug Chem

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