Chapter 3. Aims of the present study

During the past twenty years, gene therapy research has progressed from cell culture studies to extensive in vivo preclinical and human gene therapy trials. The previously used gene delivery methods have proved relatively ineffective. The main goals of gene therapy research are to develop safe and effective vectors, to develop targeted and effective methods of vector delivery into the target cells, and to find feasible methods to control transgene expression in an appropriate way to produce the desired therapeutic protein.

The main aim of the present study was to develop surgical methods for organ-specific gene transfer using an adenoviral vector for bacterial β -galactosidase reporter gene transfer in a porcine model.

The specific aims of this experimental study were:

1. to evaluate the efficiency of gene transfer into the target organs by intra-arterial infusion of vectors using pharmacological adjuvant agents,

2. to develop a surgical closed-circuit organ perfusion method for effective gene transfer into the kidney to be used in gene therapy of Alport syndrome,

3. to test the suitability of the perfusion method for gene delivery into various organs,

4. to assess the possible reactive effects on the treated organ and the systemic effects resulting from perfusion-mediated adenoviral gene delivery.