Nabel, Elizabeth G.

The field of gene transfer has developed in an era of expanding biomedical knowledge. The potential for gene transfer to treat cardiovascular disease is great, yet identified and unidentified barriers remain. Gene transfer and its ultimate application, gene therapy, require extensive details of not only the mechanism of disease but the biological implications of the vectors used to deliver the therapeutic genes as well. Many of these details are becoming available via the study of genomics. Genomics, the study of complete genetic sequences, holds the potential for enabling and amplifying the therapeutic hopes for gene transfer. Identification of new therapeutic genes, new regulatory sequences, and establishing the patterns of gene expression from tissues exposed to vectors and transgenes will rapidly advance the application of gene transfer. Finally, there are historical and ongoing lessons learned from the development of gene transfer that may be applicable to the challenging field of genomics and may enable its future success.

AbstractThis unit provides a set of protocols for introducing recombinant genes into normal, injured, and atherosclerotic arteries. The protocols include animal preparation, surgical techniques, and delivery systems. Protocols describe gene delivery to normal, injured, and stented porcine iliofemoral arteries, employing a double balloon infusion catheter to deliver the vector. Another basic protocol describes gene delivery to atherosclerotic arteries using a hyperlipidemic double‐injury rabbit model, and requires surgical exposure of the artery and instillation of the gene vector via a catheter. Additional protocols describe gene delivery to normal and injured murine carotid and femoral arteries. An describes a percutaneous method for arterial gene delivery. These protocols may be adapted to deliver genes to either injured or noninjured atherosclerotic arteries.