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 receptor-specific monoclonal antibody (MAb). This MAb acts as a molecule Trojan horse, and triggers the transport of the stealth nanocontainer across the 2 biological membrane barriers that separate the blood from the interior of brain cells. These barriers are the brain microvascular endothelial wall, which forms the blood-brain 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, 2003
- Accession Number
- ADA419493
Entities
People
- William M. Pardridge
Organizations
- University of California, Los Angeles