Chemically inactivated adenoviral vectors that can efficiently transduce target cells when delivered in the form of virus-microbead conjugates

• Published in: Gene therapy Vol. 12; no. 6; pp. 521 - 533
• Main Authors: Pandori, M W, Sano, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2005; Nature Publishing Group
• Subjects: Adenoviridae - genetics; Adenovirus; Adenoviruses; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies, Monoclonal - pharmacology; Applied cell therapy and gene therapy; Avidin - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; Biotinylation; Cell Biology; Cell Line, Tumor; Cell lines; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Design and construction; Dogs; Expression vectors; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene targeting; Gene Therapy; Genetic Therapy - methods; Genetic vectors; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Health. Pharmaceutical industry; Human Genetics; Humans; Indicators and Reagents - administration & dosage; Industrial applications and implications. Economical aspects; Infectivity; Integrin alphaV - immunology; Medical sciences; Methods; Mice; Microspheres; Nanotechnology; Neoplasms - therapy; Physiological aspects; Polymerase Chain Reaction - methods; Rats; Receptors, Virus - immunology; Receptors, Virus - metabolism; research-article; Streptavidin - administration & dosage; Transduction, Genetic - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Virus Inactivation; United States; gene delivery; biotinylation; virus targeting; microbeads (nanocarriers); lectin; adenovirus; Virus; Lectin; Adenoviridae; Targeting; Target cell; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302420

Safe and effective use of viral vectors for gene therapeutics requires versatile control over their delivery to target sites in human subjects. We have developed a strategy for the creation of adenoviral vectors that possess conditional infectivity. The adenoviral vectors used were inactivated chemically such that they had little or no ability to infect cells. However, when such chemically inactivated adenoviral vectors were conjugated to the surfaces of appropriate microbeads and the resulting adenovirus-microbead conjugates were provided with the ability to associate stably with cells, the infectivity of these adenoviral vectors was restored. For certain target cell lines, the infectivity of such adenovirus-microbead conjugates became even higher than that of free, unmodified adenoviral vectors. As a result of the chemical inactivation of viral infectivity, any adenoviral particles that become free from the microbeads should be noninfectious. Thus, these adenoviral vectors have an infectivity that is conditional: They can only infect cells, to which their microbead conjugates come into stable contact. These results lay the groundwork for the creation of targetable adenovirus-microbead conjugates with greater efficacy and safety as delivery agents for gene therapeutics.