Note: BOOK COVER -- HALF-TITLE -- TITLE -- COPYRIGHT -- DEDICATION -- CONTENTS -- PREFACE TO THE SERIES -- PREFACE -- CONTRIBUTORS -- 1. PRESENT AND FUTURE STATUS OF GENE THERAPY -- GENE THERAPY OR GENE DELIVERY? -- GENE THERAPY: A PARADIGM -- THE FUTURE OF GENE THERAPY -- A NOVEL WAY TO TREAT METABOLIC DISEASE -- RETROVIRAL VECTORS, A PROTOTYPIC GENE THERAPY SYSTEM -- DEFECTIVE VIRUSES AND TRANS-COMPLEMENTATION -- IMMUNE RESPONSES: THE BANE OF GENE THERAPY? -- A THIRD UNANTICIPATED PROBLEM: RECEPTOR EXPRESSION -- IMMUNE RESPONSES: A BOON FOR GENE THERAPY? -- WHAT FUTURE FOR GENE THERAPY? -- REFERENCES -- 2. EXPRESSION PLASMIDS FOR NON-VIRAL GENE THERAPY -- INTRODUCTION -- EXPRESSION PLASMID STRUCTURE -- Bacterial Elements -- Mammalian Transcription Unit -- Enhancer/Promoter -- 5′ Untranslated Region -- Intron -- Coding Sequence -- 3′ Untranslated Region -- Poly(A) Signal -- MULTIVALENT EXPRESSION PLASMIDS -- Multiple Transcription Units Per Plasmid -- Multicistronic mRNA (IRES-Dependent Translation) -- Alternative RNA Splicing -- IMMUNOSTIMULATORY SEQUENCES -- PERSISTENCE -- Preventing Promoter Attenuation -- Replication/Nuclear Retention -- Integration -- Immune Response -- TISSUE-SPECIFIC EXPRESSION -- Muscle -- Liver -- Lung -- Tumors -- Inducible Promoters -- DRUG-REGULATED EXPRESSION SYSTEMS -- Tetracycline System -- Rapamycin System -- Antiprogestin System -- CONCLUDING REMARKS -- REFERENCES -- 3. DNA PACKAGING IN NON-VIRAL SYSTEMS -- INTRODUCTION -- ASSEMBLY OF POLYAMINE-DNA COMPLEXES: DNA CONDENSATION -- The Morphology of Polyamine-DNA Complexes -- Phenomenological Models for DNA Condensation by Polyamines -- Quantitative Models for DNA Condensation by Polyamines -- Manning's Counterion Condensation Theory -- The Forces of DNA Condensation -- The Coil-Globule Transition as a Model for DNA Condensation -- A Kinetic Model for DNA Condensation. , DNA PACKAGING BY POLYMER CROWDING EFFECTS -- ASSEMBLY OF LIPID-DNA COMPLEXES -- Internal Model -- Electrostatic Model -- Coated Electrostatic Model -- Spaghetti and Meatball Model -- Mixed Model -- Micellar Aggregate Model -- Hydrophobic Complex Model -- LINC (lipid interactive-non condensing) Structures -- DISCUSSION -- REFERENCES -- 4. BIOLOGICAL BARRIERS TO GENE TRANSFER -- INTRODUCTION -- INTRAVENOUS ADMINISTRATION AND BARRIERS TO EXTRAVASATION -- Biodistribution of Colloidal Systems -- Interactions with Blood Components -- Biodistribution of Gene Delivery Systems -- EPITHELIAL BARRIERS -- BIODISTRIBUTION WITHIN TISSUES -- CELLULAR INTERNALIZATION -- Ligand-mediated Uptake -- INTRACELLULAR BARRIERS -- Escape from the Degradative Pathway -- Transport within the Cytoplasm -- Delivery of DNA to the Nucleus -- REFERENCES -- 5. CATIONIC LIPID-BASED GENE DELIVERY SYSTEMS -- INTRODUCTION -- DNA PLASMID DESIGN, TRANSFECTION AND GENE EXPRESSION -- PHASE BEHAVIOR OF DNA -- CATIONIC LIPIDS AND THEIR PHASE BEHAVIOR -- INTERACTIONS OF CATIONIC LIPIDS AND DNA -- STRUCTURE OF THE COMPLEXES -- GENOSOME PREPARATION -- TRANSFECTION AND GENE EXPRESSION IN VITRO AND IN VIVO -- STRUCTURE ACTIVITY RELATIONSHIPS -- CONCLUSION -- REFERENCES -- 6. THERAPEUTIC APPLICATIONS OF LIPID-BASED GENE DELIVERY SYSTEMS -- INTRODUCTION -- REQUIREMENTS FOR OPTIMAL LIPID-BASED GENE TRANSFER -- Pharmacological Considerations -- Transport from the Site of Administration to Target Tissues or Cells -- Intracellular Factors Influencing Transgene Expression from Lipoplex -- EFFECTS OF FORMULATION OF LIPID-BASED DELIVERY SYSTEMS -- Influence of Formulation -- Biological Stability and Pharmacokinetics -- Organ Specificity of Transgene Expression -- Duration of Transgene Expression -- Toxicity -- SCALE UP CONSIDERATIONS OF LIPID PREPARATIONS -- Shelf Stability -- Preparation and Manufacturing. , THERAPEUTIC APPLICATIONS OF LIPID-BASED SYSTEMS -- CONCLUSION -- REFERENCES -- 7. POLYMERIC GENE DELIVERY SYSTEMS FOR IN VIVO GENE THERAPY -- INTRODUCTION -- POLYVINYLPYRIDINIUM-BASED POLYMERS -- CHITOSAN-BASED SYSTEMS -- HYDROXYLATED NYLONS -- POLYETHYLENIMINES -- DENDRIMERS -- METHACRYLATE-BASED POLYMERS -- PINC SYSTEMS -- GELATIN-BASED SYSTEMS -- SUSTAINED RELEASE POLYMERIC SYSTEMS -- OTHER POLYMERIC SYSTEMS -- CONCLUDING REMARKS -- REFERENCES -- 8. POLYCATION-BASED DELIVERY SYSTEMS FOR RECEPTOR-MEDIATED GENE DELIVERY -- POLYELECTROLYTE REACTION AND VECTOR SELF-ASSEMBLY -- Techniques for Determination of Complex Formation -- TARGETED DELIVERY OF POLYELECTROLYTE DNA COMPLEXES TO SPECIFIC CELLS -- Transferrin-mediated Targeting -- Targeting Using the Asialoglycoprotein Receptor -- Targeting Using Other Ligand Systems -- DELIVERY OF GENES FROM THE ENDOSOME/LYSOSOME INTO THE CYTOPLASM -- Chloroquine and Other Weak Bases -- Poly(ethylene imine) and Starburst™ Dendrimers -- Influenza Virus Hemagglutinin Peptides -- Synergistic Effects of Transfection Agents -- NUCLEAR DELIVERY AND EFFICIENCY OF TRANSCRIPTION -- Direct Intracytoplasmic Injection -- Direct Intranuclear Injection -- SYSTEMIC DELIVERY OF POLYELECTROLYTE COMPLEXES -- Barriers to Successful Systemic Gene Delivery -- Nuclease Degradation of DNA in the Bloodstream -- Activation of the Complement Cascade -- Interaction with Serum Proteins -- In Vitro Analysis of Protein Binding -- Oriented Self-assembly Using Block Copolymers to Inhibit Protein Binding -- CONCLUDING REMARKS -- REFERENCES -- 9. DNA DELIVERY SYSTEMS BASED ON SYNTHETIC PEPTIDES -- INTRODUCTION -- Itinerary of a Non-viral DNA Delivery System -- Why Synthetic Peptides? -- DNA CONDENSING PEPTIDES -- Poly-(L-Lysine) -- Synthetic Cationic Peptides -- Lipophilic Cationic Peptides -- ENDOSOMOLYTIC PEPTIDES. , Influenza HA Variants and JTS-1 -- GALA -- NUCLEAR LOCALIZATION SEQUENCES -- SUMMARY AND PERSPECTIVE -- ACKNOWLEDGEMENTS -- REFERENCES -- 10. GENE-BASED VACCINES -- WHAT ARE GENE-BASED VACCINES? -- OVERVIEW OF IMMUNE RESPONSES TO VACCINES -- WHAT ARE THE SHORTCOMINGS OF ANTIGEN-BASED VACCINES? -- ADVANTAGES OF GENE-BASED VACCINES -- DESIGN AND MECHANISM OF GENE-BASED VACCINES -- Basic Design of Plasmid DNA Vaccines -- Methods of DNA Vaccine Delivery -- Nature and Mechanism of Antigen Presentation and T-Cell Responses -- Nature and Mechanism of Humoral Responses -- POTENTIAL APPLICATIONS FOR GENE-BASED VACCINES -- Prophylactic Vaccination Against Infectious Diseases -- Immunotherapeutic Vaccination for Chronic Infections -- Immunotherapy for Cancer -- OTHER CONSIDERATIONS -- Safety and Regulatory Issues -- Implications for Gene Therapy -- Gene Vaccines as a Research Tool -- REFERENCES -- 11. INTRAVASCULAR DELIVERY OF NAKED PLASMID DNA -- INTRODUCTION -- INTERSTITIAL DELIVERY TO MUSCLE -- INTRAVASCULAR DELIVERY TO MUSCLE -- INTRAVASCULAR DELIVERY TO LIVER -- CONCLUSIONS -- REFERENCES -- 12. GENE THERAPY CLINICAL TRIALS FOR CYSTIC FIBROSIS: VIRAL AND NON-VIRAL APPROACHES -- INTRODUCTION -- THE GOALS OF CF GENE THERAPY -- CF AIRWAY BIOLOGY -- CELLULAR TARGETS IN CF GENE THERAPY -- GENE TRANSFER-HOW MUCH IS ENOUGH? -- IN VIVO PRECLINICAL STUDIES -- VIRAL VECTORS -- Adenovirus -- Adeno-associated Virus (AAV) -- NON-VIRAL DELIVERY SYSTEMS -- PHASE 1 CLINICAL TRIALS: VECTORS AND DOSAGES -- Viral -- Non Viral Delivery Systems -- CRITICAL REVIEW OF RESULTS AND DESIGN -- THE WAY FORWARD -- SUMMARY -- REFERENCE -- 13. GENE THERAPY FOR CANCER: STRATEGIES AND REVIEW OF CLINICAL TRIALS -- INTRODUCTION -- METHODS FOR GENE TRANSFER INTO SOLID TUMORS -- Non-viral or DNA-Mediated Gene Transfer into Solid Tumors -- Viral-Mediated Gene Transfer into Solid Tumors. , Retroviral Vectors -- Pseudotyped Retroviral Vectors -- Adenoviral Vectors -- Second Generation Adenoviral Vectors -- Adeno-associated Viral Vectors (AAV) -- Other Viral Vectors -- GENERAL APPROACHES FOR GENE THERAPY OF SOLID TUMORS -- GENE THERAPY STRATEGIES AND CLINICAL TRIALS FOR SOLID TUMORS -- Drug Sensitivity Genes and "Suicide Genes" -- Herpes Simplex Virus Thymidine Kinase Gene Therapy -- Cytosine Deaminase Gene Therapy -- Drug Sensitivity and Suicide Gene Therapy Clinical Trials -- Immunomodulation Using Gene Therapy -- Cytokine Genes -- Granulocyte-Monocyte Colony Stimulating Factor (GM-CSF) -- Interleukin-2 (IL-2) -- Interleukin-4 (IL4) -- Interleukin-7 (IL-7) -- Interleukin-12 (IL-12) -- Interferon-gamma (INF-g) -- Tumor Necrosis Factor (TNF) -- Introduction of Major Histocompatibility Complex (MHC) Genes -- Co-stimulatory Molecules -- Tumor-Specific Antigens -- Tumor Suppressor and Oncogene Inactivation Gene Therapy -- Oncogene-Targeted Antisense Clinical Trials -- p53 Gene Therapy Clinical Trials -- SUMMARY -- REFERENCES -- INDEX.