Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer.
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.
Departments of Internal Medicine, Physiology and Biophysics, and Otolaryngology, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
R W
RW
Walters
S M
SM
Yi
S
S
Keshavjee
K E
KE
Brown
M J
MJ
Welsh
J A
JA
Chiorini
J
J
Zabner
D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006386:Hemagglutination Tests; D006801:Humans; D008561:Membrane Fusion; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*
D019158:N-Acetylneuraminic Acid