| Unnatural amino acid incorporation onto adenoviral (Ad) coat proteins facilitates chemoselective modification and retargeting of Ad type 5 vectors. | |
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MedLine Citation:
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PMID: 21613404 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Surface modification of adenovirus vectors can improve tissue-selective targeting, attenuate immunogenicity, and enable imaging of particle biodistribution, thus significantly improving therapeutic potential. Currently, surface engineering is constrained by a combination of factors, including impact on viral fitness, limited access to functionality, or incomplete control over the site of modification. Here, we report a two-step labeling process involving an initial metabolic placement of a uniquely reactive unnatural amino acid, azidohomoalanine (Aha), followed by highly specific chemical modification. As genetic modification of adenovirus is unnecessary, vector production is exceedingly straightforward. Aha incorporation demonstrated no discernible impact on either virus production or infectivity of the resultant particles. "Click" chemical modification of surface-exposed azides was highly selective, allowing for the attachment of a wide range of functionality. Decoration of human adenovirus type 5 (hAd5) with folate, a known cancer-targeting moiety, provided an ∼20-fold increase in infection of murine breast cancer cells (4T1) in a folate receptor-dependent manner. This study demonstrates that incorporation of unnatural amino acids can provide a flexible, straightforward route for the selective chemical modification of adenoviral vectors. |
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Authors:
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Partha Sarathi Banerjee; Philomena Ostapchuk; Patrick Hearing; Isaac Sheridan Carrico |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-05-25 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-07 Completed Date: 2011-09-21 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 7546-54 Citation Subset: IM |
Affiliation:
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Department of Chemistry, State University of New York at Stony Brook, 1 John Toll Road, Stony Brook, NY 11794-3400, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics* Amino Acids / chemistry* Animals Capsid Proteins / chemistry* Cell Line, Tumor Folic Acid / administration & dosage Genetic Vectors* Mass Spectrometry Mice Microscopy, Fluorescence |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI041636/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Capsid Proteins; 59-30-3/Folic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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