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.

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Preface: Molecular and Mechanical Aspects of Gene Transfer; K.L. March. Acknowledgements. Vectors and Gene Transfer Systems: Molecular Aspects of Delivery. 1. Development of Viral Vectors for Human Gene Therapy; Retrovirus and Adenovirus (Part I); B.C. Trapnell, M.N. Pensiero. 2. Adenoviruses (Part II): Improvement of Adenoviral Vectors for Human Gene Therapy: E1 and E4 Deleted Recombinant Adenoviruses; J.F. Dedieu, et al. 3. Adeno-Associated Virus and Other New DNA Virus Vectors; T.R. Floote, et al. 4. Plasmid and Other Non-Viral Vectors; L.B. Jacobsen. 5. The HVJ/Liposome Molecular Delivery System for In Vivo Genetic Engineering; G.H. Gibbons. 6. Endogenous Expression Modification: Antisense Approaches; M. Simons. Methods for Localizing Gene Transfer: Mechanical Aspects of Delivery. 7. Catheter-Based Local Drug and Gene Delivery; R.L. Wilensky. 8. Fluid Dynamics of Catheter Delivery: Effects on Delivery Efficiency and Localization; C.R. Lambert, S. Rowland. 9. Targeted and Sustained-Release Delivery Concepts in Gene Therapy; R.W. Schroff, L.L. Kunz. Gene Delivery For Local Vascular Expression. 10. Viral Vector-Based Vascular Gene Delivery: Basic Studies and Therapeutic Applications; E.G. Nabel. 11. Cell-Based Vascular Gene Delivery: Endothelial Cells as Carriers; J. Burke, et al. 12. Cell-Based Gene Delivery: Smooth Muscle Cells as Carriers; A.W. Clowes. 13. Vascular Cell Proliferation Dynamics: Implications for Gene Transfer and Restenosis; R.S. Schwartz, et al.14. Angiogenesis and Collateral Formation; J.M. Isner. Gene Delivery for Local Cardiac Expression. 15. Cell-Based Myocardial Protein Delivery; M.H. Soonpaa, L.J. Field. 16. Skeletal Myoblast Therapy in Cardiovascular Disease; D.A. Taylor, et al. 17. Adenovirus and the Myocardium; J.A. Towbin. Gene Delivery for Systemic Expression. 18. Gene Delivery for Systemic Expression: Plasmid, Retroviral, and Adenoviral Approaches; K. Parker Ponder. 19. Adenoviral Gene Delivery Approaches for Systemic Expression; S.C. Stevenson, A. McClelland. 20. Experimental Approaches Using Kallikrein Gene Therapy for Hypertension; J. Chao, L. Chao. Biophysical Considerations in Vector Delivery. 21. Pharmacokinetics of Local Vector Delivery to Vascular Tissues: Implications for Efficiency and Localization; K.L. March, B. Trapnell. Color Plates. Index.