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Screening for Neutralizing Antibodies Against Natural and Engineered AAV Capsids in Nonhuman Primate Retinas

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Retinal Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1715))

Abstract

Adeno-associated virus (AAV) has shown promise as a therapeutic gene delivery vector for inherited retinal degenerations in both preclinical disease models and human clinical trials. The retinas of nonhuman primates (NHPs) share many anatomical similarities to humans and are an important model for evaluating AAV gene delivery. Recent evidence has shown that preexisting immunity in the form of neutralizing antibodies (NABs) in NHPs strongly correlates with weak or lack of AAV transduction in the retina when administered intravitreally, work with translational implications. This necessitates prescreening of NHPs before intravitreal delivery of AAV. In this chapter, we describe a method for screening NHP serum for preexisting NABs.

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Acknowledgments

We thank the members of both the Flannery and Schaffer labs including M.A. Kotterman for her work on the development of the serum screen. This work was funded by NIH 5R01EY022975.

Author information

Authors and Affiliations

  1. The Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA

    Timothy P. Day, Leah C. Byrne, John G. Flannery & David V. Schaffer

  2. Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Leah C. Byrne

  3. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA

    John G. Flannery & David V. Schaffer

  4. Vision Science Graduate Group, School of Optometry, University of California, Berkeley, CA, USA

    John G. Flannery

  5. Department of Bioengineering, University of California, Berkeley, CA, USA

    David V. Schaffer

  6. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA

    David V. Schaffer

Authors
  1. Timothy P. Day
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  2. Leah C. Byrne
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  3. John G. Flannery
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  4. David V. Schaffer
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Corresponding author

Correspondence to David V. Schaffer .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    Camiel J.F. Boon

  2. Department of Ophthalmology, Leiden University Medical Center (LUMC), Leiden, The Netherlands

    Jan Wijnholds

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Day, T.P., Byrne, L.C., Flannery, J.G., Schaffer, D.V. (2018). Screening for Neutralizing Antibodies Against Natural and Engineered AAV Capsids in Nonhuman Primate Retinas. In: Boon, C., Wijnholds, J. (eds) Retinal Gene Therapy. Methods in Molecular Biology, vol 1715. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7522-8_17

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  • DOI: https://doi.org/10.1007/978-1-4939-7522-8_17

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7521-1

  • Online ISBN: 978-1-4939-7522-8

  • eBook Packages: Springer Protocols

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