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

Gene Therapy volume 12, pages 521–533 (2005)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Fred Winston for access to his light/fluorescence microscope and for helpful suggestions on microscopic analysis. We also thank Dr Yuwadee Watanapokasin for help with quantitative PCR analysis. MWP was supported by a postdoctoral fellowship from the US Army Prostate Cancer Research Program, Department of Defense (DAMD17-99-9510), and by a training grant from the National Cancer Institute (CA59367; awarded to Dr Melvin E Clouse). This work was supported, in part, by grants from the National Cancer Institute (CA86262) and the US Army Breast Cancer Research Program, Department of Defense (DAMD17-03-1-0192).

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  1. Center for Molecular Imaging Diagnosis and Therapy and Basic Science Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    M W Pandori & T Sano

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Pandori, M., Sano, T. Chemically inactivated adenoviral vectors that can efficiently transduce target cells when delivered in the form of virus-microbead conjugates. Gene Ther 12, 521–533 (2005). https://doi.org/10.1038/sj.gt.3302420

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