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Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers

  • Nicole N. Thadani
    Nicole N. Thadani
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
  • Joanna Yang
    Joanna Yang
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
    More by Joanna Yang
  • Buhle Moyo
    Buhle Moyo
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
    More by Buhle Moyo
  • Ciaran M. Lee
    Ciaran M. Lee
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
  • Maria Y. Chen
    Maria Y. Chen
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
  • Gang Bao
    Gang Bao
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
    More by Gang Bao
  • , and 
  • Junghae Suh*
    Junghae Suh
    Department of Bioengineering, Rice University, Houston, Texas 77030, United States
    Department of Biosciences, Rice University, Houston, Texas 77030, United States
    Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas 77030, United States
    Systems, Synthetic and Physical Biology Program, Rice University, Houston, Texas 77030, United States
    *Email: [email protected]
    More by Junghae Suh
Cite this: ACS Synth. Biol. 2020, 9, 3, 461–467
Publication Date (Web):February 18, 2020
https://doi.org/10.1021/acssynbio.9b00341
Copyright © 2020 American Chemical Society

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    Abstract

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    Adeno-associated virus (AAV) is widely favored as a gene therapy vector, tested in over 200 clinical trials internationally. To improve targeted delivery a variety of genetic capsid modifications, such as insertion of targeting proteins/peptides into the capsid shell, have been explored with some success but larger insertions often have unpredictable deleterious impacts on capsid formation and gene delivery. Here, we demonstrate a modular platform for the integration of exogenous peptides and proteins onto the AAV capsid post-translationally while preserving vector functionality. We decorated the AAV capsid with leucine-zipper coiled-coil binding motifs that exhibit specific noncovalent heterodimerization. AAV capsids successfully display hexahistidine tagged-peptides using this approach, as demonstrated through nickel column affinity. This protein display platform may facilitate the incorporation of biological moieties on the AAV surface, expanding possibilities for vector enhancement and engineering.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acssynbio.9b00341.

    • Quantification of zipper incorporation in Velcro-AAV; E3 Velcro-AAV transduction in HUVECs; Velcro-AAV nickel affinity column chromatography elution fraction quantification (PDF)

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    Cited By

    This article is cited by 4 publications.

    1. Ruth Frenkel, Dana Tribby, Boris Boumajny, Nicholas Larson, Matthew Sampson, Christopher Barney, Svetlana Bergelson, Zoran Sosic, Bernice Yeung. ACUVRA: Anion-Exchange Chromatography UV-Ratio Analysis—A QC-Friendly Method for Monitoring Adeno-Associated Virus Empty Capsid Content To Support Process Development and GMP Release Testing. The AAPS Journal 2023, 25 (1) https://doi.org/10.1208/s12248-022-00768-0
    2. Amaury Pupo, Audry Fernández, Siew Hui Low, Achille François, Lester Suárez-Amarán, Richard Jude Samulski. AAV vectors: The Rubik’s cube of human gene therapy. Molecular Therapy 2022, 30 (12) , 3515-3541. https://doi.org/10.1016/j.ymthe.2022.09.015
    3. Hanna J. Wagner, Wilfried Weber, Martin Fussenegger. Synthetic Biology: Emerging Concepts to Design and Advance Adeno‐Associated Viral Vectors for Gene Therapy. Advanced Science 2021, 8 (9) https://doi.org/10.1002/advs.202004018
    4. Kübra Kaygisiz, Christopher V. Synatschke. Materials promoting viral gene delivery. Biomaterials Science 2020, 8 (22) , 6113-6156. https://doi.org/10.1039/D0BM01367F

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