Combination of Electroporation and DNA/Dendrimer Complexes Enhances Gene Transfer into Murine Cardiac Transplants

doi:10.1034/j.1600-6143.2001.10408.x

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Wiley InterScience

American Journal of Transplantation

Volume 1 Issue 4, Pages 334 - 338

Published Online: 5 Apr 2002

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Combination of Electroporation and DNA/Dendrimer Complexes Enhances Gene Transfer into Murine Cardiac Transplants

Yinong Wang ^a,1 , Yalai Bai ^a,1 , Christopher Price ^a , Peter Boros ^a , Lihui Qin ^a , Anna U. Bielinska ^b , Jolanta F. Kukowska-Latallo ^b , James R. Baker Jr ^b and Jonathan S. Bromberg ^a, *

^a Institute for Gene Therapy and Molecular Medicine and the Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA ^b Center for Biologic Nanotechnology, The University of Michigan, Ann Arbor, MI 48105, USA

*Corresponding author: Jonathan S. Bromberg, jon.bromberg@mountsinai.org

¹ Present address: Department of Surgery (Cardiothoracic), Yale University School of Medicine, 333 Cedar Street, 121 FMB, New Haven, CT 06510.

KEYWORDS

Dendrimer • electroporation, gene transfer, transplantation

ABSTRACT

Electroporation is a new gene delivery method to increase gene transfer and expression in vivo. Starburst polyamidoamine dendrimers have been demonstrated to augment gene expression in vitro and in vivo. We hypothesized that the combination of electroporation and dendrimer could enhance the gene transfer and gene expression in cardiac transplants. After immersion in DNA/dendrimer complexes or intracoronary transfer of DNA/dendrimer complexes, both nonvascularized and vascularized syngeneic cardiac grafts, respectively, were subjected to serial electrical pulses before transplantation. β-Galactosidase reporter gene expression in the graft was determined by X-Gal staining. Gene expression was enhanced 10- to 45-fold in grafts immersed in DNA/dendrimer complexes, or after intracoronary transfer of DNA/dendrimer complexes, and subjected to 20 square wave 25-ms pulses with a strength of 200 V/cm. The combination of electroporation and DNA/dendrimer complexes may provide a novel approach to enhance gene transfer and gene expression ex vivo.

Received 11 April 2001, revised and accepted for publication 21 June 2001

DIGITAL OBJECT IDENTIFIER (DOI)

10.1034/j.1600-6143.2001.10408.x About DOI