Engineering novel cell surface receptors for virus-mediated gene transfer

John H Lee; Tracy J Baker; Lara K Mahal; Joseph Zabner; Carolyn R Bertozzi; David F Wiemer; Michael J Welsh

doi:10.1074/jbc.274.31.21878

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Engineering novel cell surface receptors for virus-mediated gene transfer

Journal article

Open access

Peer reviewed

Engineering novel cell surface receptors for virus-mediated gene transfer

John H Lee, Tracy J Baker, Lara K Mahal, Joseph Zabner, Carolyn R Bertozzi, David F Wiemer and Michael J Welsh

The Journal of biological chemistry, Vol.274(31), pp.21878-21884

07/30/1999

DOI: 10.1074/jbc.274.31.21878

PMID: 10419507

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Abstract

The absence of viral receptors is a major barrier to efficient gene transfer in many cells. To overcome this barrier, we developed an artificial receptor based on expression of a novel sugar. We fed cells an unnatural monosaccharide, a modified mannosamine that replaced the acetyl group with a levulinate group (ManLev). ManLev was metabolized and incorporated into cell-surface glycoconjugates. The synthetic sugar decorated the cell surface with a unique ketone group that served as a foundation on which we built an adenovirus receptor by covalently binding biotin hydrazide to the ketone. The artificial receptor enhanced adenoviral vector binding and gene transfer to cells that are relatively resistant to adenovirus infection. These data are the first to suggest the feasibility of a strategy that improves the efficiency of gene transfer by using the biosynthetic machinery of the cell to engineer novel sugars on the cell surface.

Endothelium, Vascular - cytology

Gene Transfer Techniques

Adenoviridae

Biotin - pharmacokinetics

Humans

Cells, Cultured

Hexosamines - pharmacokinetics

Umbilical Veins

Endothelium, Vascular - physiology

Streptavidin - pharmacokinetics

Animals

Transfection - methods

beta-Galactosidase - biosynthesis

Models, Biological

Mice

Receptors, Cell Surface - biosynthesis

Receptors, Cell Surface - physiology

Kinetics

beta-Galactosidase - genetics

Genetic Vectors

3T3 Cells

Genes, Reporter

Biotin - analogs & derivatives

Details

Title: Subtitle: Engineering novel cell surface receptors for virus-mediated gene transfer
Creators: John H Lee
Tracy J Baker
Lara K Mahal
Joseph Zabner
Carolyn R Bertozzi
David F Wiemer
Michael J Welsh
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.274(31), pp.21878-21884
DOI: 10.1074/jbc.274.31.21878
PMID: 10419507
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: DK25295 / NIDDK NIH HHS
Language: English
Date published: 07/30/1999
Academic Unit: Neuroscience and Pharmacology; Chemistry; Internal Medicine
Record Identifier: 9983985919302771

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