James M' Wilson, MD, Ph'D'

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• James M. Wilson, MD, Ph.D.
• Head, Gene Therapy Program
• Julie Johnston, Ph.D.
• Director, Penn Vector Core

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Penn Vector Core

• Main Function
• - To develop and produce vectors for
  investigators for basic research and preclinical
  studies
• Scope of Services
• - Construction of new custom vectors
• - Large scale preparation of custom vectors
• - Quality control for small and large animal
  models
• - Provision of ready-to-use reporter gene vectors
• - Short-term facility usage and consultation

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Penn Vector Core
Adenoviral Vectors
Lentiviral Vectors
AAV Vectors
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Penn Vector Preclinical Production Capacity
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AAV Vector Production by Serotype
1000
800
Other serotypes
AAV2/9
AAV2/8
AAV2/7
600
AAV2/6 and 2/6.2
AAV2/5
AAV2/1
AAV2
400
200
0
2000
2001
2002
2003
2004
2005
2006
2007
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Development of Novel AAV Vectors

• Natural Diversity as a Source for Novel Capsids
• Generation of AAV Vectors by Rational Design
• Directed Evolution to Overcome Host Restriction

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Graded Release Criteria for non-GLP
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Transduction of Airway Cells by AAV Serotype
Vectors
AAV2/5
AAV2/6
AAV2/6.2
Human airway cells
Mouse lungs
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Systemic Delivery of AAV Serotype Vectors to
Mice (1E11GC)
Day 90
Day 3
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Systemic Delivery of AAV Serotype Vectors to Mice
AAV2
AAV5
AAV7
AAV8
AAV9
1011
Heart
1012
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Summary for Tissue Specific Expressional
Targeting by rAAV9
Promoter (specificity)
Heart
Liver
Pancreas
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Acknowledgments

• Wilson Lab
• Dr. Guang-ping Gao
• Dr. Luk Vandenberghe
• Dr. Maria Limberis
• NHBLI Gene Therapy Resource Program