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J. Biol. Chem., Vol. 276, Issue 23, 20610-20616, June 8, 2001
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From the Departments of Recombinant adeno-associated viruses (AAV) are
promising gene therapy vectors. Whereas AAV serotype 2-mediated gene
transfer to muscle has partially replaced factor IX deficiency in
hemophilia patients, its ability to mediate gene transfer to the lungs
for cystic fibrosis is hindered by lack of apical receptors. However, AAV serotype 5 infects human airway epithelia from the lumenal surface.
We found that in contrast to AAV2, the apical membrane of airway
epithelia contains abundant high affinity receptors for AAV5. Binding
and gene transfer with AAV5 was abolished by genetic or enzymatic
removal of sialic acid from the cell surface. Furthermore, binding and
gene transfer to airway epithelia was competed by lectins that
specifically bind 2,3-linked sialic acid. These observations suggest
that 2,3-linked sialic acid is either a receptor for AAV5 or it is a
necessary component of a receptor complex. Further elucidation of the
receptor for this virus should enhance understanding of parvovirus
biology and expand the therapeutic targets for AAV vectors.
Binding of Adeno-associated Virus Type 5 to 2,3-Linked Sialic
Acid Is Required for Gene Transfer*
§¶,
,,§¶§§,
Internal Medicine,
§ Physiology and Biophysics, and Otolaryngology,
¶ Howard Hughes Medical Institute, University of Iowa College of
Medicine, Iowa City, Iowa 52242, the ** Toronto Lung Transplant
Program, University of Toronto, Toronto, Ontario M5G 2C4, Canada,
and the Hematology Branch, NHLBI and
¶¶ Gene Therapeutics Branch, NIDCR, National Institutes of
Health, Bethesda, Maryland 20892
*
This work was supported by Center for Gene Therapy,
NIDDKD, National Institutes of Health Grant T30DK54759, the Cystic
Fibrosis Foundation, and the Roy J. Carver Charitable Trust.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University
of Iowa College of Medicine, 500 EMRB, Iowa City, IA 52242. Tel.:
319-353-5511; Fax: 319-335-7623; E-mail:
joseph-zabner@uiowa.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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