Non-Invasive Gene Therapy of Experimental Parkinson's Disease
Abstract
The present research has developed a non-viral gene targeting technology, whereby the effects of a neurotoxin on the brain can be reversed shortly after the intravenous injection of a therapeutic gene medicine without the use of viral vectors. The brain gene targeting technology developed in this work creates an artificial virus which is comprised of non-immunogenic lipids and proteins, wherein the therapeutic gene is packaged in the interior of the gene delivery vehicle, which is called a pegylated immunoliposome (PIL). The PIL carrying the gene is a 85 nm stealth nanocontainer, which is relatively invisible to the body s reticuloendothelial system, which normally removes nanocontainers from the blood. The surface of the nanocontainer is studded with a receptorspecific monoclonal antibody (MAb). This MAb acts as a moleculr Trojan horse, and triggers the transport of the stealth nanocontainer across the 2 biologicial membrane barriers that separate the blood from the interior of brain cells. These barriers are the brain microvascular endothelial wall, which forms the bloodbrain barrier in vivo, and the brain cell plasma membrane. Both barriers express the transferrin receptor, and the anti-receptor MAb enables the PIL to cross the membrane barriers via normal physiological transport processes usually used for endogeneous ligands such as transferrin. With this approach non-viral, non-invasive gene therapy of the brain is now possible.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA462348
Entities
People
- William M. Pardridge
Organizations
- University of California, Los Angeles