Document Detail


Site-Specific Modification of Adeno-Associated Viruses via a Genetically Engineered Aldehyde Tag.
MedLine Citation:
PMID:  23038676     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
As a consequence of their well-defined nanostructure and intrinsic bioactive functionality, virus-based nanoparticles have shown promise for mediating gene delivery. Adeno-associated virus (AAV) nanoparticles, which possess an excellent safety profile and therapeutic potential, hold potential for use in human gene therapy. However, because of their native tropisms, the applicability of AAV nanoparticles is often limited to restricted ranges of cells or tissues. Thus, retargeting AAV particles to the desired cell populations has continued to be a major research focus in many gene therapy applications. In this study, a general strategy is reported for nanoparticle targeting. This involves the site-specific modification of AAV type 2 (AAV2) by genetically incorporating a short peptide, in this case an aldehyde tag, in the viral capsid. Such a tag can be exploited for site-specific attachment of targeting molecules and allows for further introduction of targeting antibodies or ligands. It is shown that this modification neither affects the level of infectious viral titer nor intracellular trafficking properties. Furthermore, the site-specific conjugation of targeting antibodies could significantly enhance viral transduction to those target cells that have otherwise exhibited very low permissiveness to AAV2 infection. This method also allows the functional incorporation of RGD peptides onto AAV2 for enhanced delivery with implications for cancer gene therapy.
Authors:
Yarong Liu; Yun Fang; Yu Zhou; Ebrahim Zandi; Chi-Lin Lee; Kye-Il Joo; Pin Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-5
Journal Detail:
Title:  Small (Weinheim an der Bergstrasse, Germany)     Volume:  -     ISSN:  1613-6829     ISO Abbreviation:  Small     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235338     Medline TA:  Small     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Department of Chemical Engineering and Material Science, University of Southern California, 3710 McClintock Ave, Los Angeles, CA 90089, USA.
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