Preclinical Study Design for rAAV

  • Terence R. FlotteEmail author
  • Thomas J. Conlon
  • Christian Mueller
Part of the Methods in Molecular Biology book series (MIMB, volume 807)


The process of moving a novel drug such as an adeno-associated viral vector from the bench top to bedside is an arduous process requiring coordination and skill from multiple laboratories and regulatory agencies. Proceeding to a phase I safety trial in humans after most of the proof-of-concept data have been acquired may take several years. During this time, agencies including the FDA, NIH Office of Biotechnology Activities (OBA), and Recombinant DNA Advisory Committee (RAC) along with the investigator’s team will develop a series of preclinical toxicology and biodistribution studies in order to develop a safety profile for the intended novel drug. In this chapter, key features of the pharm–tox study design and conduct will be discussed. Highlighted features include choosing a sufficient animal number and species to use in testing, dose determination, typical toxicological assays performed, the use of Standard Operating Procedures in respect to good laboratory practices compliancy, and role of the Quality Assurance Unit.

Key words

AAV gene therapy Preclinical testing AAV toxicology Vector biodistribution Good laboratory practices 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Terence R. Flotte
    • 1
    Email author
  • Thomas J. Conlon
    • 2
  • Christian Mueller
    • 3
  1. 1.Department of PediatricsUniversity of Massachusetts Medical School Gene Therapy CenterWorcesterUSA
  2. 2.Department of PediatricsUniversity of Florida Powell Gene Therapy CenterGainesvilleUSA
  3. 3.Department of PediatricsUniversity of Massachusetts Medical SchoolWorcesterUSA

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