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Journal of Drug Delivery
Volume 2011 (2011), Article ID 296151, 12 pages
http://dx.doi.org/10.1155/2011/296151
Review Article

The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier

1Department of Medicine, UCLA, Warren Hall 13-164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
2ArmaGen Technologies, Inc., Santa Monica, CA 90401, USA

Received 5 July 2011; Revised 4 September 2011; Accepted 4 September 2011

Academic Editor: Abdelwahab Omri

Copyright © 2011 Ruben J. Boado and William M. Pardridge. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The application of blood-borne gene therapy protocols to the brain is limited by the presence of the blood-brain barrier (BBB). Viruses have been extensively used as gene delivery systems. However, their efficacy in brain is limited by the lack of transport across the BBB following intravenous (IV) administration. Recent progress in the “Trojan Horse Liposome” (THL) technology applied to transvascular non-viral gene therapy of the brain presents a promising solution to the trans-vascular brain gene delivery problem. THLs are comprised of immunoliposomes carrying nonviral gene expression plasmids. The tissue target specificity of the THL is provided by peptidomimetic monoclonal antibody (MAb) component of the THL, which binds to specific endogenous receptors located on both the BBB and on brain cellular membranes, for example, insulin receptor and transferrin receptor. These MAbs mediate (a) receptor-mediated transcytosis of the THL complex through the BBB, (b) endocytosis into brain cells and (c) transport to the brain cell nuclear compartment. The expression of the transgene in brain may be restricted using tissue/cell specific gene promoters. This manuscript presents an overview on the THL transport technology applied to brain disorders, including lysosomal storage disorders and Parkinson's disease.