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Systemic Delivery of Adeno-Associated Viral Vectors in Mice and Dogs

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Viral Vectors for Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1937))

Abstract

Many diseases affect multiple tissues and/or organ systems, or affect tissues that are broadly distributed. For these diseases, an effective gene therapy will require systemic delivery of the therapeutic vector to all affected locations. Adeno-associated virus (AAV) has been used as a gene therapy vector for decades in preclinical studies and human trials. These studies have shown outstanding safety and efficacy of the AAV vector for gene therapy. Recent studies have revealed yet another unique feature of the AAV vector. Specifically, AAV can lead to bodywide gene transfer following a single intravascular injection. Here we describe the protocols for effective systemic delivery of AAV in both neonatal and adult mice and dogs. We also share lessons we learned from systemic gene therapy in the murine and canine models of Duchenne muscular dystrophy.

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Acknowledgments

The research on systemic AAV delivery in the Duan lab was supported by the National Institutes of Health (NS-90634, AR-70517 and AR-69085 ), Department of Defense (MD150133), Jesse’s Journey-The Foundation for Gene and Cell Therapy, Hope for Javier, Jackson Freel DMD Research Fund and Solid Biosciences Inc. The authors thank Keqing Zhang for the assistance in figure preparation.

Disclosure: D.D. is a member of the scientific advisory board, an equity holder of Solid Biosciences, LLC. D.D. is an inventor on a patent licensed to Solid Biosciences, LLC.

Author information

Authors and Affiliations

  1. Department of Veterinary Pathobiology, College of Veterinary Medicine, The University of Missouri, Columbia, MO, USA

    Lakmini P. Wasala & Dongsheng Duan

  2. Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO, USA

    Chady H. Hakim, Yongping Yue & Dongsheng Duan

  3. National Center for Advancing Translational Sciences, NIH, Rockville, MD, USA

    Chady H. Hakim & N. Nora Yang

  4. Department of Neurology, School of Medicine, The University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  5. Department of Bioengineering, The University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  6. Department of Biomedical Sciences, College of Veterinary Medicine, The University of Missouri, Columbia, MO, USA

    Dongsheng Duan

Authors
  1. Lakmini P. Wasala
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  2. Chady H. Hakim
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  3. Yongping Yue
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  4. N. Nora Yang
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  5. Dongsheng Duan
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Corresponding author

Correspondence to Dongsheng Duan .

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Editors and Affiliations

  1. Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA

    Fredric P. Manfredsson

  2. Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI, USA

    Matthew J. Benskey

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Wasala, L.P., Hakim, C.H., Yue, Y., Yang, N.N., Duan, D. (2019). Systemic Delivery of Adeno-Associated Viral Vectors in Mice and Dogs. In: Manfredsson, F., Benskey, M. (eds) Viral Vectors for Gene Therapy. Methods in Molecular Biology, vol 1937. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9065-8_18

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  • DOI: https://doi.org/10.1007/978-1-4939-9065-8_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9064-1

  • Online ISBN: 978-1-4939-9065-8

  • eBook Packages: Springer Protocols

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