Gene Transfer in the Cardiovascular System, Softcover reprint of the original 1st ed. 1997
Experimental Approaches and Therapeutic Implications
Developments in Cardiovascular Medicine Series, Vol. 189

The goal of gene transfer is protein expression. a process brought about by the insertion of a gene coding for a foreign protein into target cells resulting in the synthesis of the foreign protein For gene therapy, a tmnsferred therapeutic gene must be expressed at a level beneficial for the patient. This chapter provides an introductory overview of the rapidly evolving field of non-viral approaches for gene delivery to rnarnrnalian cells. Although currently there are fewer ongoing clinical trials using non-viral approaches than those using viral based systems, the number of non-viral trials is increasing. The long range goal of some research groups is the development of a genetically engineered artificial virus targeted to specific cells in the human body. An arurual conference, organized by Cambridge Healthtech Institute entitled "Artificial Self-Assembling Systems for Gene Transfer", brings together researchers interested in this field [1]. Assembly of an artificial virus is very complex; other research groups aim to develop simpler delivery systems consisting of a plasmid combined with delivery agents. Viral-based systems are very successful for gene delivery, but despite their successes, viral-based systems have some geneml limitations and system-specific limitations. When employing a viml-based system, the following limitations should be considered: ? size limitation of the inserted gene due to packaging constraints (e. g. adenovirus, retrovirus) . ? potential tumorigenesis (e. g. retrovirus) ? potential for insertional mutagenesis (greater than plasmid based systems) ? potential imrnunogenicity (e. g.

Vectors and Gene Transfer Systems: Molecular Aspects of Delivery.- 1. Development of Viral Vectors for Human Gene Therapy: Retrovirus and Adenovirus (Part I).- 2. Adenoviruses (Part II): Improvement of Adenoviral Vectors for Human Gene Therapy: E1 and E4 Deleted Recombinant Adenoviruses.- 3. Adeno-associated Virus and Other New DNA Virus Vectors.- 4. Plasmid and Other Non-Viral Vectors.- 5. The HVJ/Liposome Molecular Delivery System for In Vivo Genetic Engineering.- 6. Endogenous Expression Modification: Antisense Approaches.- Methods for Localizing Gene Transfer: Mechanical Aspects of Delivery.- 7. Catheter-Based Local Drug and Gene Delivery.- 8. Fluid Dynamics of Catheter Delivery: Effects on Delivery Efficiency and Localization.- 9. Targeted and Sustained-Release Delivery Concepts in Gene Therapy.- Gene Delivery for Local Vascular Expression.- 10. Viral Vector-Based Vascular Gene Delivery: Basic Studies and Therapeutic Applications.- 11. Cell-Based Vascular Gene Delivery: Endothelial Cells as Carriers.- 12. Cell-Based Gene Delivery: Smooth Muscle Cells as Carriers.- 13. Vascular Cell Proliferation Dynamics: Implications for Gene Transfer and Restenosis.- 14. Angiogenesis and Collateral formation.- Gene Delivery for Local Cardiac Expression.- 15. Cell-Based Myocardial Protein Delivery.- 16. Skeletal Myoblast Therapy in Cardiovascular Disease.- 17. Adenovirus and the Myocardium.- Gene Delivery for Systemic Expression.- 18. Gene Delivery for Systemic Expression: Plasmid, Retroviral, and Adenoviral Approaches.- 19. Adenoviral Gene Delivery Approaches for Systemic Expression.- 20. Experimental Approaches Using Kallikrein Gene Therapy for Hypertension.- Biophysical Considerations in Vector Delivery.- 21.Pharmacokinetics of Local Vector Delivery To Vascular Tissues: Implications for Efficiency and Localization.- Color Plates.