This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arbetman, A. E.
Right arrow Articles by Colosi, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arbetman, A. E.
Right arrow Articles by Colosi, P.

 Previous Article  |  Next Article 

Journal of Virology, December 2005, p. 15238-15245, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15238-15245.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Novel Caprine Adeno-Associated Virus (AAV) Capsid (AAV-Go.1) Is Closely Related to the Primate AAV-5 and Has Unique Tropism and Neutralization Properties

Alejandra E. Arbetman,1* Michael Lochrie,1 Shangzhen Zhou,1 Jennifer Wellman,1 Ciaran Scallan,1 Mohammad M. Doroudchi,1 Britta Randlev,1 Susannah Patarroyo-White,1 Tongyao Liu,1 Peter Smith,1 Howard Lehmkuhl,2 Lea Ann Hobbs,2 Glenn F. Pierce,1 and Peter Colosi1

Avigen, Inc., Alameda, California 94502,1 Respiratory Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 500102

Received 16 June 2005/ Accepted 22 September 2005

Preexisting humoral immunity to adeno-associated virus (AAV) vectors may limit their clinical utility in gene delivery. We describe a novel caprine AAV (AAV-Go.1) capsid with unique biological properties. AAV-Go.1 capsid was cloned from goat-derived adenovirus preparations. Surprisingly, AAV-Go.1 capsid was 94% identical to the human AAV-5, with differences predicted to be largely on the surface and on or under the spike-like protrusions. In an in vitro neutralization assay using human immunoglobulin G (IgG) (intravenous immune globulin [IVIG]), AAV-Go.1 had higher resistance than AAV-5 (100-fold) and resistance similar to that of AAV-4 or AAV-8. In an in vivo model, SCID mice were pretreated with IVIG to generate normal human IgG plasma levels prior to the administration of AAV human factor IX vectors. Protein expression after intramuscular administration of AAV-Go.1 was unaffected in IVIG-pretreated mice, while it was reduced 5- and 10-fold after administration of AAV-1 and AAV-8, respectively. In contrast, protein expression after intravenous administration of AAV-Go.1 was reduced 7.1-fold, similar to the 3.8-fold reduction observed after AAV-8administration in IVIG-pretreated mice, and protein expression was essentially extinguished after AAV-2 administration in mice pretreated with much less IVIG (15-fold). AAV-Go.1 vectors also demonstrated a marked tropism for lung when administered intravenously in SCID mice. The pulmonary tropism and high neutralization resistance to human preexisting antibodies suggest novel therapeutic uses for AAV-Go.1 vectors, including targeting diseases such as cystic fibrosis. Nonprimate sources of AAVs may be useful to identify additional capsids with distinct tropisms and high resistance to neutralization by human preexisting antibodies.

* Corresponding author. Mailing address: 1301 Harbor Bay Parkway, Alameda, CA 94502-6541. Phone: (510) 748-7263. Fax: (510) 748-7136. E-mail: AArbetman{at}Avigen.com.

Journal of Virology, December 2005, p. 15238-15245, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15238-15245.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Grimm, D., Lee, J. S., Wang, L., Desai, T., Akache, B., Storm, T. A., Kay, M. A. (2008). In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses. J. Virol. 82: 5887-5911 [Abstract] [Full Text]  
  • Qiu, J., Cheng, F., Pintel, D. J. (2006). Expression Profiles of Bovine Adeno-Associated Virus and Avian Adeno-Associated Virus Display Significant Similarity to That of Adeno-Associated Virus Type 5. J. Virol. 80: 5482-5493 [Abstract] [Full Text]  
  • Scallan, C. D., Jiang, H., Liu, T., Patarroyo-White, S., Sommer, J. M., Zhou, S., Couto, L. B., Pierce, G. F. (2006). Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood 107: 1810-1817 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»