Gene Transfer in the Cardiovascular System

1. Front Matter

   Pages i-xx

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2. Vectors and Gene Transfer Systems: Molecular Aspects of Delivery

   1. Front Matter

      Pages 1-1

      PDF

   2. Development of Viral Vectors for Human Gene Therapy: Retrovirus and Adenovirus (Part I)

      • Bruce C. Trapnell, Michael N. Pensiero

      Pages 3-24

   3. Adenoviruses (Part II): Improvement of Adenoviral Vectors for Human Gene Therapy: E1 and E4 Deleted Recombinant Adenoviruses

      • J. F. Dedieu, E. Vigne, C. Orsini, P. Denefle, M. Perricaudet, P. Yeh

      Pages 25-55

   4. Adeno-Associated Virus and Other New DNA Virus Vectors

      • Terence R. Flotte, Sandra A. Afione, Barry J. Byrne, B. Helen

      Pages 57-83

   5. Plasmid and Other Non-Viral Vectors

      • Linda B. Jacobsen

      Pages 85-110

   6. The HVJ-Liposome Molecular Delivery System for In Vivo Genetic Engineering

      • Gary H. Gibbons

      Pages 111-141

   7. Endogenous Expression Modification: Antisense Approaches

      • Michael Simons

      Pages 143-175

3. Methods for Localizing Gene Transfer: Mechanical Aspects of Delivery

   1. Front Matter

      Pages 177-177

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   2. Catheter Based Local Drug and Gene Delivery

      • Robert L. Wilensky

      Pages 179-199

   3. Fluid Dynamics of Catheter Delivery: Effects on Delivery Efficiency and Localization

      • Charles R. Lambert, Stephen Rowland

      Pages 201-217

   4. Targeted and Sustained-Release Delivery Concepts in Gene Therapy

      • Robert W. Schroff, Lawrence L. Kunz

      Pages 219-236

4. Gene Delivery for Local Vascular Expression

   1. Front Matter

      Pages 237-237

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   2. Viral Vector-Based Vascular Gene Delivery: Basic Studies and Therapeutic Applications

      • Elizabeth G. Nabel

      Pages 239-253

   3. Cell-Based Vascular Gene Delivery: Endothelial Cells as Carriers

      • James Burke, John Ojeifo, James A. Zwiebel

      Pages 255-278

   4. Cell — Based Gene Delivery: Smooth Muscle Cells as Carriers

      • Alexander W. Clowes

      Pages 279-292

   5. Vascular Cell Proliferation Dynamics: Implications for Gene Transfer and Restenosis

      • Robert S. Schwartz, Aloysius Chu, Myung Ho Jeong, Michael E. Staab, Sanjay S. Srivatsa, Vincent J. Pompili et al.

      Pages 293-306

   6. Angiogenesis and Collateral Formation

      • Jeffrey M. Isner

      Pages 307-330

5. Gene Delivery for Local Cardiac Expression

   1. Front Matter

      Pages 331-331

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   2. Cell-Based Myocardial Protein Delivery

      • Mark H. Soonpaa, Loren J. Field

      Pages 333-353

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.

• DNA
• cardiovascular
• gene therapy
• gene transfer
• genes

• Krannert Institute of Cardiology, Indiana University Medical Center, Indianapolis, USA

  Keith L. March

• R. L. Roudebush VA Medical Center, Indianapolis, USA

  Keith L. March

Policies and ethics