Chemically inactivated adenoviral vectors that can efficiently transduce target cells when delivered in the form of virus-microbead conjugates.
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.
Pandori
M W
MW
Center for Molecular Imaging Diagnosis and Therapy and Basic Science Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Sano
T
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001360:Avidin / Q000494:pharmacology; D019921:Biotinylation; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents / Q000008:administration & dosage; D039564:Integrin alphaV / Q000276:immunology; D051379:Mice; D008863:Microspheres; D009369:Neoplasms / Q000628:therapy*; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism; D019809:Streptavidin / Q000008:administration & dosage; D014161:Transduction, Genetic / Q000379:methods*; D038301:Virus Inactivation
D000911:Antibodies, Monoclonal; C568771:CLMP protein, human; C568772:CLMP protein, mouse; C568773:Clmp protein, rat; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D007202:Indicators and Reagents; D039564:Integrin alphaV; D011991:Receptors, Virus; D001360:Avidin; D019809:Streptavidin