Biodefense Vaccines, Therapeutics and Diagnostics

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• Biodefense Vaccines, Therapeutics and Diagnostics
• NGIC Workshop
• September 27, 2004
• Robert L. McKown, Ph.D.

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What is Biotechnology?
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What is Biotechnology?

• Recombinant genetic Engineeringusing biological
  process to develop products
• G. Steven Burrill 1997

Genetic Engineering
Product
Raw Materials
Living System
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Enabling Technology
Recombinant DNA Technology Boyer and Cohen, 1973
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The Birth of an Industry
University of California, San Francisco
Genentech Inc. South San Francisco
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Founded April 7, 1976 Herbert Boyer and Robert
Swanson
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Proof of Concept

• Cloning the human insulin gene
• Cloned by Genentech scientists in 1978
• Licensed to Eli Lilly
• First recombinant drug marketed, 1982
• Product revenues from human insulin (humulin)
  reached 900 million in 2003

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The Promise of Biotechnology
DNA
PROTEIN
Bioproduction of molecules so complex they can
only be synthesized in a living system
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Biotech Products
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The JMU Biomanufacturing Laboratory

• Concept document created in 1997
• Development funding awarded in 1998
• Lab space committed in 1999
• Lab design and set up in 2000
• Became operational in 2001

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Founding Sponsors
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Biomanufacturing Technology

• Genetic manipulations and analysis
• Cell line development
• Fermentation and cell culture technology
• Product purification technology
• Quality assurance and quality control
• Regulatory guidelines and compliance
• Process development

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The Production Platform
                                                 
         
Cell Line Development
 
Systems Management Regulatory Affairs Quality
Assurance
Production
Product Recovery
Quality Control Analytical Testing Documentation
Product Analysis
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Development of Expression Systems
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Cell Line Development
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Production and Purification
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Product Analysis
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Proof of ConceptCloning, Expression,
Purificationof Green Fluorescence Protein (GFP)
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Purification of GFP
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Analysis of GFP
                                             
 
Fraction I II III
IV STD
Mol. Wt.   94,000   67,000 43,000 30,000   20,10
0   14,400
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Projects and Collaborations

• Lacritin project, UVA and EyeRx
• Vaccine and diagnostics projects, USAMRIID
• Staphylococcus aureus Protein A project,
  Genentech, Inc.
• New River Pharmaceuticals project
• M. tuberculosis project, Veterans Hospital, Long
  Beach, CA

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Research and Development of a Recombinant Protein
(Lacritin) as a New Therapeutic for Treatment for
Dry Eye Syndrome
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Lacritin and the Lacrimal Gland

• A stable, novel human tear glycoprotein
• Produced primarily by the lacrimal gland located
  on the upper eyelid
• Also found in salivary glands and the thyroid

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Properties of Lacritin Demonstrated in Cell
Culture

• Lacritin hydrates the corneal surface as a
  natural component of tears
• Lacritin causes the rapid, sustained release of
  calcium in cultured corneal epithelial cells
• Lacritin stimulates proliferation of ductal cells

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Potential as a Therapeutic Agent

• Dry Eye Syndrome
• Caused by the decrease in both the quality and
  volume of tear secretion
• Affects over 35 million Americans
• The application of eye drops is the primary
  current treatment
• Lacritin as a Potential Therapeutic
• Promotion of tear production
• Induction of cell proliferation

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Research History

• Lacritin gene discovered and characterized by the
  Gordon Laurie lab at UVA
• JMU collaboration with the Laurie lab
• Engineered a recombinant mature lacritin gene
  that was cloned, expressed, and purified
• Current Research
• Creation of C-terminal deletions to identify
  domains of biological activity
• Lacritin protein in pre-clinical animal studies
  for treatment of Dry Eye Syndrome

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Future Applications of Biotechnology

• New Human Therapeutics and Vaccines
• New Human Diagnostics
• New Genetically Engineered Microbes, Plants, and
  Animals
• New Biomaterials (Rubber, Plastics, Spider Silk)
• Genetically Engineered Humans?

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Acknowledgements

• Robert McKown, Ph.D., JMU
• Ron Raab, Ph.D., JMU
• George Coffman, Ph.D., JMU
• Gordon Laurie, Ph.D., UVA
• Jeremy Goodin, Ph.D., USAMRIID
• Patricia Williams, Ph.D., EyeRx
• JMU Students