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Adeno-Associated Viral Vectors for CF Gene Therapy

  • Terence R. Flotte
  • Isabel Virella-Lowell
  • Kye A. Chesnut
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 70)

Abstract

AAV is a nonpathogenic human parvovirus that has a natural mechanism for long-term persistence in human cells. Wild-type AAV is unique in that it undergoes stable integration of its DNA into a specific region of human chromosome 19, the AAVS1 site (1, 2, 3, 4), a process that our group has also recently described in vivo in rhesus macques (5). This site specificity appears to be mediated by specific interactions between the nonstructural protein, Rep, and the sequence-specific binding elements within the AAVS1 site (6). AAV vectors have been developed by deleting the two AAV genes, rep and cap from the viral genome, and substituting transgenes such as CFTR (7,8). Since the rep gene is deleted, these vectors generally do not integrate in a site-specific manner, yet they do persist long-term in mammalian cells through a complicated process that involves both episomal persistence and random-site integration (9, 10, 11).

Keywords

Cystic Fibrosis Fetal Bovine Serum Medium Vector Genome Biological Titer Infectious Center Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Terence R. Flotte
    • 1
  • Isabel Virella-Lowell
    • 1
  • Kye A. Chesnut
    • 1
  1. 1.Powell Gene Therapy CenterUniversity of FloridaGainesville

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