Doenecke, Axel and Kroemer, Alexander and Scherer, Marcus N. and Schlitt, Hans-Juergen and Geissler, Edward K. (2010) AAV plasmid DNA simplifies liver-directed in vivo gene therapy: comparison of expression levels after plasmid DNA-, adeno-associated virus- and adenovirus-mediated liver transfection. JOURNAL OF GENE MEDICINE, 12 (10). pp. 810-817. ISSN 1099-498X, 1521-2254
Full text not available from this repository. (Request a copy)Abstract
Background Successful liver gene therapy depends on efficient gene transfer techniques and long-lasting gene expression after successful transfer. Over the last decades, important progress has been made with the introduction of viral vectors using animal models, although their use is hampered by a complex and costly preparation compared to the simple and cost-effective preparation of plasmid DNA. These problems become even more critical when considering the application of viral vectors in human gene therapy and gene therapy trials. In a previous study, we were able to show that the hydrodynamics-based gene transfer of plasmid-DNA, containing the adeno-associated-virus specific inverted terminal repeats (AAV-ITR), prolongs gene expression in the liver, although it remained unclear whether plasmid gene transfer could achieve similar expression levels compared to viral-vector gene transfer. Methods Rat livers were transfected in-vivo with AAV-ITR-containing plasmid-DNA using a modified hydrodynamics-based procedure. Expression levels were monitored thereafter and compared with expression levels after viral-vector gene transfer. Results A high and stable long-term expression was achieved after in vivo transfection of rat livers with AAV-ITR-containing plasmids. The expression course resembled that after AAV-mediated gene transfer, and the expression was at least as high, and lasted as long, compared to recombinant AAV-mediated gene transfer. Conclusions We consider AAV-ITR-containing plasmids as a simple and cost-effective alternative to recombinant viral vectors, especially for liver-directed gene therapy in rodents. With ongoing progress in gene transfer methods for naked DNA, these plasmids may also become a successful alternative to recombinant viral vectors in human gene therapy. Copyright (C) 2010 John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LONG-TERM EXPRESSION; TAIL VEIN INJECTION; TRANSGENE EXPRESSION; SKELETAL-MUSCLE; VIRAL VECTORS; NAKED DNA; HUMAN ALPHA-1-ANTITRYPSIN; HYDRODYNAMIC INJECTION; ALLOGRAFT SURVIVAL; IMMUNE-RESPONSE; AAV plasmid; in vivo gene therapy; naked DNA gene transfer; nonviral gene transfer |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jul 2020 10:43 |
| Last Modified: | 09 Jul 2020 10:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24087 |
Actions (login required)
 |
View Item |
