Direct selection of targeted adenovirus vectors by random peptide display on the fiber knob.
Gene Ther
; 14(20): 1448-60, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17700705
Targeting of gene transfer at the level of cell entry is one of the most attractive challenges in vector development. However, attempts to redirect adenovirus vectors to alternative receptors by engineering the capsid-coding region have shown limited success because proper targeting ligand-receptor systems on the cells of interest are generally unknown. Systematic approaches to generate adenovirus vectors targeting any given cell type need to be developed to achieve this goal. Here, we constructed an adenovirus library that was generated by a Cre-lox-mediated in vitro recombination between an adenoviral fiber-modified plasmid library and genomic DNA to display random peptides on a fiber knob. As proof of concept, we screened the adenovirus display library on a glioma cell line and observed selection of several particular peptide sequences. The targeted vector carrying the most frequently isolated peptide significantly enhanced gene transduction in the glioma cell line but not in many other cell lines. Because the insertion of a pre-selected peptide into a fiber knob often fails to generate an adenovirus vector, the selection of targeting peptides is highly useful in the context of the adenoviral capsid. This vector-screening system can facilitate the development of a targeted adenovirus vector for a variety of applications in medicine.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN Viral
/
Adenoviridae
/
Biblioteca de Péptidos
/
Proteínas de la Cápside
/
Vectores Genéticos
Tipo de estudio:
Clinical_trials
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido