Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

Back

Plasmid DNA-based Gene Transfer with Ultrasound and Microbubbles

Author(s): Yoshiaki Taniyama, Junya Azuma, Hiromi Rakugi, Ryuichi Morishita.

Abstract:

Gene therapy offers a novel approach for the prevention and treatment of a variety of diseases, but it is not yet a common option in the real world because of various problems. Viral vectors show high efficiency of gene transfer, but they have some problems with toxicity and immunity. On the other hand, plasmid DNA-based gene transfer is very safe, but its efficiency is relatively low. Especially, plasmid DNA gene therapy is used for cardiovascular disease because plasmid DNA transfer is possible for cardiac or skeletal muscle. Clinical angiogenic gene therapy using plasmid DNA gene transfer has been attempted in patients with peripheral artery disease, but a Phase III clinical trial did not show sufficient efficiency. Recently, a Phase III clinical trial of hepatocyte growth factor gene therapy in peripheral artery disease (PAD) showed improvement of ischemic ulcers, but it could not salvage limbs from amputation. In addition, a Phase I/II clinical study of fibroblast growth factor gene therapy in PAD extended amputation-free survival, but it seemed to fail in Phase III. In this situation, we and others have developed plasmid DNA-based gene transfer using ultrasound with microbubbles to enhance its efficiency while maintaining safety. Ultrasound-mediated gene transfer has been reported to augment the gene transfer efficiency and select the target organ using cationic microbubble phospholipids which bind negatively charged DNA. Ultrasound with microbubblesis likely to create new therapeutic options inavariety of diseases.

Keywords: Angiogenesis, gene therapy, peripheral artery disease (PAD), ultrasound, microbubble, cavitation

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 11
ISSUE: 6
Year: 2011
Page: [485 - 490]
Pages: 6
DOI: 10.2174/156652311798192851
Price: $58