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
Services
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 Ghosh, D.
Right arrow Articles by Barry, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ghosh, D.
Right arrow Articles by Barry, M. A.

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 13667-13672, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13667-13672.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Selection of Muscle-Binding Peptides from Context-Specific Peptide-Presenting Phage Libraries for Adenoviral Vector Targeting

Debadyuti Ghosh1,2 and Michael A. Barry1,2,3*

Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children's Hospital, Houston, Texas,1 Departments of Molecular and Human Genetics and Immunology, Baylor College of Medicine, Houston, Texas,3 Department of Bioengineering, Rice University, Houston, Texas2

Received 24 September 2004/ Accepted 2 August 2005

Production of cell-targeting vectors in part involves the addition of new targeting ligands to the vector to mediate binding to the cells of interest. For viral vectors, the ideal approach is to genetically engineer new ligands into the capsid proteins of the virus to generate a single agent to mediate therapy. Although this is ideal, this insertion of an exogenous ligand from one structural context into the differing structural context of a capsid protein can ablate the function of the ligand or disrupt viral assembly and function. To address this context problem for adenoviral vectors, we have engineered a "context-specific" peptide-presenting phage library. We have displayed a 12-amino-acid (12-mer) random peptide library between the H and I sheets of the fiber protein of adenovirus type 5 on the pIII protein of fd bacteriophage. This library was used for peptide selection against C2C12 mouse skeletal muscle cells. Five rounds of selection combined with four rounds of clearing on nontarget cells selected one primary peptide designated 12.51, which bound target C2C12 cells approximately 100-fold better than the positive control RGD peptide. Translation of 12.51 back into the fiber protein produced a ligand-modified adenoviral vector that mediated 14-fold-better transduction of target C2C12 cells. These data suggest context-specific peptide-presenting libraries may allow selection of compatible peptide ligands for functional translation into viral vectors for retargeting.

* Corresponding author. Mailing address: One Baylor Plaza, BCM505, Houston, TX 77030. Phone: (713) 798-5959. Fax: (713) 798-1481. E-mail: mab{at}bcm.edu.

Journal of Virology, November 2005, p. 13667-13672, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13667-13672.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Aartsma-Rus, A., van Ommen, G.-J. B. (2007). Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications. RNA 13: 1609-1624 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»