AAV Vector Development Milestones

The Vector Core at Nationwide Children’s has historically demonstrated a commitment to constantly improving its services and providing gene transfer vectors of extremely high quality.  The following list of Vector Core milestones documents Nationwide Children’s contributions to the field of AAV vector development.

  • The CMF produces two phase I clinical AAV products, the first was an AAV2 product approved in Great Britain by the MHRA (FDA equivalent) to treat a congenital blindness disorder called choroideremia.12 The second was an AAV1 product approved by the FDA in October 2011, with a phase I trial initiated at Nationwide Children’s Hospital in February 2012.
  • The CMF initiated clinical production of its first drug substance in support of an IND application.
  • The CMF produced a tox lot for an AAV1 gene therapy product that was used to support a recently approved IND.
  • The CMF successfully produces an AAV gene therapy tox product for testing in a GLP tox study to support an IND application.
  • A Nationwide Children’s Hospital internal initiative to fund a cGMP clinical manufacturing facility is approved. The five-year, multi-million dollar plan provides for facility, equipment and full-time employee infrastructure.
1998 - 2006
  • In 1998, the research Viral Vector Core was established to support pre-clinical SIV/HIV genetic vaccine studies using stable producer cell line technology.
  • Using plasmid DNA transfection methodology, the Vector Core successfully produces of pre-clinical vector to support a National Institute of Neurological Disorders and Stroke sponsored U54 Project for development of two AAV-based biologics towards IND application.  The Vector Core meets all associated milestones.
  • Nationwide Children’s develops the first stable rAAV producer cell lines and Ad hybrid production methods in 1996 3,5,6,9.
  1. Chen, C-L., R. L. Jensen, B. C. Schnepp, M. J. Connell, R. Shell, T. J. Sferra, J. S. Bartlett, K. R. Clark, and P. R. Johnson.  2005. Molecular Characterization of Adeno-Associated Viruses in ChildrenJ Virol 79: 14781–14792.
  2. Clark, K. R., X. Liu, J. P. McGrath, and P. R. Johnson. 1999. Highly purified recombinant adeno-associated virus vectors are biologically active and free of detectable helper and wild-type virusesHum Gene Ther 10:1031-1039.
  3. Clark, K. R., F. Voulgaropoulou, D. M. Fraley, and P. R. Johnson. 1995. Cell lines for the production of recombinant adeno-associated virusHum Gene Ther 6:1329-1341.
  4. Clark, K. R., F. Voulgaropoulou, and P. R. Johnson. 1996. A stable cell line carrying adenovirus-inducible rep and cap genes allows for infectivity titration of adeno-
  5. Liu, X., F. Voulgaropoulou, R. Chen, P. R. Johnson, and K. R. Clark. 2000. Selective Rep-Cap gene amplification as a mechanism for high-titer recombinant AAV production from stable cell linesMol Ther 2:394-403.
  6. Liu, X. L., K. R. Clark, and P. R. Johnson. 1999. Production of recombinant adeno-associated virus vectors using a packaging cell line and a hybrid recombinant adenovirusGene Ther 6:293-299.
  7. Rodino-Klapac LR, Janssen PM, Montgomery CL, Coley BD, Chicoine LG, Clark KR, Mendell JR. 2007. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy.  J of Transl Med, 5:45.
  8. Schnepp, B., K. Clark, D. Klemanski, C. A. Pacak, and P. R. Johnson. 2003. Genetic Fate of Recombinant Adeno-Associated Virus Vector Genomes in Muscle. J Virol 77:3495-3504.
  9. Schnepp, B., and K. R. Clark. 2002.Highly purified recombinant adeno-associated virus vectors. Preparation and quantitationMethods Mol Med 69:427-443.
  10. Schnepp, B., R. L. Jensen, C-L Chen, P. R. Johnson and K. R. Clark. 2005. Characterization of Adeno-Associated Virus Genomes Isolated from Human Tissues. J Virol 79: 14793–14803.
  11. Schnepp BC, Jensen RL, Clark KR, and Johnson PR. 2009.  Infectious molecular clones of adeno-associated virus isolated directly from human tissues.  J Virol 83:1456-1464.
  12. TouchOncology.com "Viral Vector Holds Key in Treating Genetic Blindness Disorder"