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Recombinant Baculovirus as a Highly Potent Vector for Gene Therapy of Human Colorectal Carcinoma: Molecular Cloning, Expression, and In Vitro Characterization

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Abstract

Present therapeutic strategies for most cancers are restricted mainly to the primary tumors and are also not very effective in controlling metastatic states. Alternatively, gene therapy can be a potential option for treating such cancers. Currently mammalian viral-based cancer gene therapy is the most popular approach, but the efficacy has been shown to be quite low in clinical trials. In this study, for the first time, the insect cell-specific baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has been evaluated as a vector for gene delivery to colorectal cancer cells. Experiments involving factorial design were employed to study the individual and combined effects of different parameters such as multiplicity of infection (MOI), viral incubation time and epigenetic factors on transduction efficiency. The results demonstrate that baculovirus gene delivery system holds immense potential for development of a new generation of highly effective virotherapy for colorectal, as well as other major carcinomas (breast, pancreas, and brain), and offers significant benefits to traditional animal virus-based vectors with respect to safety concerns.

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Acknowledgments

We gratefully acknowledge the assistance received from the Natural Sciences and Engineering Research Council of Canada (NSERC) to Dr. S. Prakash. A.P. acknowledges financial support from Fonds de la recherche en santé du Québec (FRSQ), Quebec, Canada. A.K. acknowledges the Alexander Graham Bell Post Graduate Scholarship—Doctoral from NSERC. M.M. acknowledges the support of the McGill Faculty of Medicine Internal Scholarship. The authors would like to thank B. Boulay, R. Tran, and J. Montes from National Research Council Canada (NRC-BRI) for their technical advice and assistance.

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Authors and Affiliations

  1. Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada

    Arghya Paul, Barbara A. Jardin, Arun Kulamarva, Meenakshi Malhotra & Satya Prakash

  2. Process Development, Sanofi Pasteur, Connaught Campus, 1755 Steeles Avenue West, Toronto, ON, M2R 3T4, Canada

    Cynthia B. Elias

  3. Centre for Biorecognition and Biosensors, Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada

    Cynthia B. Elias & Satya Prakash

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  1. Arghya Paul
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  2. Barbara A. Jardin
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  3. Arun Kulamarva
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  4. Meenakshi Malhotra
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Correspondence to Satya Prakash.

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Arun Kulamarva and Meenakshi Malhotra contributed equally to this work.

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Paul, A., Jardin, B.A., Kulamarva, A. et al. Recombinant Baculovirus as a Highly Potent Vector for Gene Therapy of Human Colorectal Carcinoma: Molecular Cloning, Expression, and In Vitro Characterization. Mol Biotechnol 45, 129–139 (2010). https://doi.org/10.1007/s12033-010-9248-7

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