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Glycan binding avidity determines the systemic fate of adeno-associated virus type 9.

Publication ,  Journal Article
Shen, S; Bryant, KD; Sun, J; Brown, SM; Troupes, A; Pulicherla, N; Asokan, A
Published in: J Virol
October 2012

Glycans are key determinants of host range and transmissibility in several pathogens. In the case of adeno-associated viruses (AAV), different carbohydrates serve as cellular receptors in vitro; however, their contributions in vivo are less clear. A particularly interesting example is adeno-associated virus serotype 9 (AAV9), which displays systemic tropism in mice despite low endogenous levels of its primary receptor (galactose) in murine tissues. To understand this further, we studied the effect of modulating glycan binding avidity on the systemic fate of AAV9 in mice. Intravenous administration of recombinant sialidase increased tissue levels of terminally galactosylated glycans in several murine tissues. These conditions altered the systemic tropism of AAV9 into a hepatotropic phenotype, characterized by markedly increased sequestration within the liver sinusoidal endothelium and Kupffer cells. In contrast, an AAV9 mutant with decreased glycan binding avidity displayed a liver-detargeted phenotype. Altering glycan binding avidity also profoundly affected AAV9 persistence in blood circulation. Our results support the notion that high glycan receptor binding avidity appears to impart increased liver tropism, while decreased avidity favors systemic spread of AAV vectors. These findings may not only help predict species-specific differences in tropism for AAV9 on the basis of tissue glycosylation profiles, but also provide a general approach to tailor AAV vectors for systemic or hepatic gene transfer by reengineering capsid-glycan interactions.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2012

Volume

86

Issue

19

Start / End Page

10408 / 10417

Location

United States

Related Subject Headings

  • Virology
  • Vibrio cholerae
  • Rats
  • Protein Binding
  • Polysaccharides
  • Mice, Inbred BALB C
  • Mice
  • Maackia
  • Liver
  • Kupffer Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shen, S., Bryant, K. D., Sun, J., Brown, S. M., Troupes, A., Pulicherla, N., & Asokan, A. (2012). Glycan binding avidity determines the systemic fate of adeno-associated virus type 9. J Virol, 86(19), 10408–10417. https://doi.org/10.1128/JVI.01155-12
Shen, Shen, Kelli D. Bryant, Junjiang Sun, Sarah M. Brown, Andrew Troupes, Nagesh Pulicherla, and Aravind Asokan. “Glycan binding avidity determines the systemic fate of adeno-associated virus type 9.J Virol 86, no. 19 (October 2012): 10408–17. https://doi.org/10.1128/JVI.01155-12.
Shen S, Bryant KD, Sun J, Brown SM, Troupes A, Pulicherla N, et al. Glycan binding avidity determines the systemic fate of adeno-associated virus type 9. J Virol. 2012 Oct;86(19):10408–17.
Shen, Shen, et al. “Glycan binding avidity determines the systemic fate of adeno-associated virus type 9.J Virol, vol. 86, no. 19, Oct. 2012, pp. 10408–17. Pubmed, doi:10.1128/JVI.01155-12.
Shen S, Bryant KD, Sun J, Brown SM, Troupes A, Pulicherla N, Asokan A. Glycan binding avidity determines the systemic fate of adeno-associated virus type 9. J Virol. 2012 Oct;86(19):10408–10417.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2012

Volume

86

Issue

19

Start / End Page

10408 / 10417

Location

United States

Related Subject Headings

  • Virology
  • Vibrio cholerae
  • Rats
  • Protein Binding
  • Polysaccharides
  • Mice, Inbred BALB C
  • Mice
  • Maackia
  • Liver
  • Kupffer Cells