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Mosaic vectors comprised of modified AAV1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells

Gene Therapy volume 13, pages 926–931 (2006)Cite this article

Abstract

Vascular-targeted gene therapies have the potential to treat many of the leading causes of mortality in the western world. Unfortunately, these therapies have been ineffective due to poor vascular gene transfer. The use of alternative virus serotypes and the incorporation of vascular targeting ligands into vectors has resulted in only modest increases in vascular gene transfer. Adeno-associated virus (AAV) 1 has shown the most promise among the AAV vectors for the transduction of vascular endothelial cells. However, no straightforward small-scale purification strategy exists for AAV1 as it does for AAV2 making it difficult to quickly produce AAV1 vector for analysis. Here we have combined two AAV1 capsid protein modifications to enhance vascular gene transfer and allow easy purification of vector particles. Mosaic vector particles have been produced comprised of capsid proteins containing the well-characterized RGD4C modification to target integrins present on the vasculature, and capsid proteins containing a modification that permits metabolic biotinylation and efficient purification of mosaic particles by avidin affinity chromatography. We show that the RGD modification results in a 50–100-fold enhancement in endothelial cell gene transfer that is maintained in biotinylated mosaic AAV1 particles. These results suggest that mosaic virions hold significant promise for targeted gene delivery to the vasculature.

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Authors and Affiliations

  1. Gene Therapy Center, Columbus Children's Research Institute, Columbus Children's Hospital, Columbus, OH, USA

    M D Stachler & J S Bartlett

  2. Integrated Biomedical Graduate Program and Medical Scientist Program, The Ohio State University, Columbus, OH, USA

    M D Stachler

  3. Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    J S Bartlett

  4. Division of Molecular Medicine, Department of Pediatrics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    J S Bartlett

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  1. M D Stachler
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Correspondence to J S Bartlett.

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Stachler, M., Bartlett, J. Mosaic vectors comprised of modified AAV1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells. Gene Ther 13, 926–931 (2006). https://doi.org/10.1038/sj.gt.3302738

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  • DOI: https://doi.org/10.1038/sj.gt.3302738

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