Chapter 1: Executive Summary
Introduction to Gene Therapy
The Status of Gene Therapy
Technology Trends
- Gene Transfer Methods
- Delivery Products
- Target Cells
- Antisense
Disease Targets
- 94 Clinical Trials Approved in the U.S.
Strategies for the Successful Development of Gene Therapy Products
The Market for Gene Therapy Products
Chapter 2: Introduction to Gene Therapy
Scope and Methodology
Definition
- Classic Gene Therapy
- Antisense Drugs and Triple Helix Technology
- Catalytic Ribozymes
A Primer on Molecular Biology
- Structure of the Genome
- The Language of Genes
- Proteins Constructed Through Intermediary or Messenger RNA
Chapter 3: Technology
The Status of Gene Therapy
- Ex Vivo and In Vivo Approaches
The Challenges of Gene Therapy
- Immunorejection
- Activation of Introduced Genes
- Achieving Sufficient Gene Transfer
- Cost
- Safety
Classic Gene Therapy
Viral Vectors
- Adenoviruses
- Adeno-associated Virus
- Herpesviruses
- Hybrid Viral Delivery Vehicles
- Retroviruses
- Sindbis Virus
- Vaccinia Virus
- Receptor-Targeted Gene Delivery
Concerns and Problems With Viral Vectors
Alternatives to Viral Gene Therapy
Synthetic Receptors
Synthetic Vectors
Muscle Cells as Gene Factories
Physical DNA Transfer Methods
- Aerosolization
- Electroporation
- Eukaryotic Layered Vector System
- The Gene Gun
- Liposomes
- Mammalian Artificial Minichromosomes
- Microencapsulation
- Microinjection
- Naked DNA
- Plasmids
Delivery Products
- Antibodies
- Antigens
- Cytokines
- Multiple-Drug-Resistance Genes
- Suicide Genes
- Tumor Suppressor Genes and Oncogenes
- Vascular Endothelial Growth Factor
Target Cells
Antisense Drugs and Triple Helix Technology
Antisense
- Potentially Applicable to 80% of All Diseases
- Switching Off Genes That Have Gone Awry
- Cost Effectiveness
- Oligonucleotides
- Antisense RNA
- Aptamers
- Genetic Antisense
- Triplex Technology
Catalytic Ribozymes
- Ribozymes Degrade Target DNA
- Making RNA Degradation Specific
Advantages of Ribozyme Technology Over Antisense
Chapter 4: Disease Targets and Research Status for Gene Therapy
Disease Targets by Company
94 Clinical Trials in Progress in the U.S.
European Gene Therapy Trials
Selected Approved Classic Gene Therapy and Antisense Protocols
- ADA Deficiency
- Anemia
- Cancer
- Astrocytoma
- Breast Cancer
- Brain Tumor
- Central Nervous System Malignancies
- Colon Cancer
- Colorectal Cancer
- Glioblastoma
- Head and Neck Tumors
- Leptomeningeal Carcinomatosis
- Leukemia
- Liver Cancer
- Lung Cancer
- Malignant Glioma
- Malignant Mesothelioma
- Melanoma
- Neuroblastoma
- Ovarian Cancer
- Prostate Cancer
- Renal Cell Carcinoma
- Solid Tumors
- Cardiovascular Disease
- Familial Hypercholesterolemia
- Peripheral Artery Disease
- Cystic Fibrosis
- Cytomegalovirus
- Gaucher’s Disease
- HIV Infection and AIDS
- Hunter’s Syndrome
- Papilloma Virus
- Rheumatoid Arthritis
Disease Targets in Research
- AIDS
- Alzheimer’s Disease
- Arthritis
- Cachexia
- Cancer
- Non-Hodgkins Lymphoma
- Prostate Cancer
- Chronic Granulomatous Disease
- Diabetes
- Fragile X Syndrome
- Gaucher’s Disease
- Gyrate Atrophy
- Hemophilia
- Hepatitis
- Herpes Simplex Virus
- Malaria
- Muscular Dystrophy
- Parkinson’s Disease
- Restenosis
- Retinal Degeneration
- Sickle Cell Anemia
Chapter 5: Issues and Trends
The Human Genome Project
- International Genome Projects
- The National Institutes of Health Support of Gene Therapy
Conditions for Which Specific Genes Have Been Identified
Strategies for the Successful Development of Gene Therapy Products
- The “Gene Club”
- Collaborative Agreements with Commercial Diagnostics Companies
- The Multivector Approach
- Genomics
- Investors Bullish on Genomics
- Probationary Alliances
- Japanese Alliances
Regulatory Issues
- Moral and Safety Issues Addressed
- Reimbursement
- Recombinant DNA Advisory Committee
- The Food and Drug Administration
- Strategies to Successfully Receive RAC and FDA Approval
- The Advent of the Clinical/Regulatory Consultant
- Steps in the Gene Therapy Viral Vector Development Process
- Patent Protection
- Companies Arise to Facilitate Academic Technology Transfer
Chapter 6: The Market
Methodology
Notes on the Data
Timing
Size of the Market for Leading Diseases
- AIDS and AIDS-Associated Diseases
- Cytomegalovirus
- HIV
Cancer
- Breast Cancer
- Colon Cancer
- Colorectal Cancer
- Kidney Cancer
- Liver Cancer
- Lung Cancer
- Melanoma
- Ovarian Cancer
- Prostate Cancer
- Solid Tumors
Cystic Fibrosis
Size of the Market for Other Diseases
- Alzheimer’s Disease
- Cardiovascular Disorders
- Familial Hypercholesterolemia
- Restenosis
- Diabetes
- Gaucher’s Disease
- Hemophilia
- Hepatitis B
- Parkinson’s Disease
- Rheumatoid Arthritis
Chapter 7: Corporate Profiles
Agracetus, Inc.
- History and Lines of Business
- Financial Information (for W.R. Grace)
- Products
- Corporate Strategies
AntiVirals, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Applied Immune Sciences, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Avigen, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Canji, Inc.
- History and Lines of Business
- Products
- Research and Development
- Corporate Strategies
Cell Genesys, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Darwin Molecular Corporation
- History and Lines of Business
- Financial Information
- Research and Development
- Corporate Strategies
GeneMedicine, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
Genetic Therapy, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Genome Therapeutics Corp.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
GenVec, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Human Genome Sciences, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
The Immune Response Corporation
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Incyte Pharmaceuticals, Inc.
- History and Lines of Business
- Financial Information
- Products
- BPI
- Protease Nexin-1
- Human Galaptin L-14-1
- Research and Development
- Corporate Strategies
Introgen Therapeutics, Inc.
- History and Lines of Business
- Products
- Research and Development
MicroProbe Corporation
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Millennium Pharmaceuticals, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Ribozyme Pharmaceuticals, Inc.
- History and Lines of Business
- Research and Development
- Corporate Strategies
Sequana Therapeutics, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
Somatix Therapy Corporation
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Targeted Genetics Corporation
- History and Lines of Business
- Financial Information
- Products
- Corporate Strategies
Transkaryotic Therapies Inc.
- History and Lines of Business
- Products
- Corporate Strategies
Viagene, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Vical, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Zynaxis, Inc.
- History and Lines of Business
- Financial Information
- Products
- Research and Development
- Corporate Strategies
Appendix A: Agencies and Associations
American Genetic Association
American Institute for Medical and Biological Engineering
American Society of Human Genetics
(Also known as Genetics Society of America)
Center for Biologics Evaluation and Research
Human Genome Organization
National Center for Human Genome Research
(Oversees U.S. contributions to the Human Genome Project)
National Eye Institute
National Heart, Lung and Blood Institute
National Institute of Allergy and Infectious Diseases
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Recombinant DNA Advisory Committee
U.S. Department of Energy
Appendix B: Company Names and Addresses
Agracetus, Inc. (A wholly owned subsidiary of W.R. Grace)
Ajinomoto Company
Antivirals, Inc.
Applied Biosystems Inc.
Applied Immune Sciences, Inc.
Ariad Pharmaceuticals Inc.
Athena Diagnostics (Formerly Genica Pharmaceuticals)
Avigen, Inc.
Baxter Biotech (A division of Baxter International Inc.)
Biogen Inc.
Boron Biologicals, Inc.
Bristol-Myers Squibb Company
British Technology Group USA
Burroughs Wellcome Company (A division of Wellcome Plc)
Canji Inc.
Cell Genesys Inc.
CellPro Inc.
Chiron Corporation
CLIN/REGS Associates
Collaborative Research (See Genome Therapeutics)
Darwin Molecular Corporation
Eli Lilly and Company
Enzo Biochem, Inc.
Gen-Probe, Inc.
GeneMedicine, Inc.
Genentech, Inc.
Genespan Corporation
Genetic Therapy, Inc.
Genetics Institute, Inc.
Genetix Pharmaceuticals, Inc.
Genica Pharmaceuticals (See Athena Diagnostics)
Genome Therapeutics
Genta Inc.
GenVec Inc.
Genzyme, Inc.
Gilead Sciences
Glaxo Holdings Plc
Green Cross Corporation
Hoffmann-La Roche Inc.
Human Genome Sciences Inc.
Hybridon, Inc.
Imclone Systems Inc.
The Immune Response Corporation
Immunex Corporation
Ingenex Inc. (A Titan Pharmaceuticals company)
Integrated Genetics Inc.
Introgen Therapeutics
Isis Pharmaceuticals Inc.
Lynx Therapeutics, Inc.
Matritech Inc.
Megabios Corporation
Merck and Company
Microbiological Associates, Inc.
MicroProbe Corporation
Millennium Pharmaceuticals Inc.
Myriad Genetics Inc.
NeXagen, Inc.
Oncogene Science Inc.
Pfizer, Inc.
PharmaGenics, Inc.
RPR Gencell (A division of Rhone-Poulenc Rorer Inc.)
Research Corporation Technologies
Rhone-Poulenc Rorer Inc.
Ribozyme Pharmaceuticals, Inc.
Ribozyme Technology Inc. (A division of Sandoz Pharmaceuticals Corporation)
Sandoz Pharmaceuticals Corporation
Schering-Plough Corporation
Sequana Therapeutics
SmithKline Beecham Corporation (A division of SmithKline Beecham Plc)
Somatix Therapy Corporation
Stem Cell Sciences
Syntex Corporation
Synthecell
SyStemix Inc.
Targeted Genetics Corporation (A subsidiary of Immunex Corporation)
Theragen (See GenVec)
Transgene SA
Transkaryotic Therapies Inc.
Triplex Pharmaceutical Corporation
The Upjohn Company
Viagene, Inc.
Vical Inc.
Virogenetics Corporation
Wellcome Plc
Zynaxis, Inc.
