Finding a safe way to get therapeutic genes past the blood-brain barrier has led to some interesting approaches using the barrier's own transport systems to shuttle DNA across the blood capillary wall from the bloodstream into the brain. The challenge that has arisen in these efforts is to protect the DNA as it makes its way through the circulation. William Pardridge and Ningya Shi of the University of California, Los Angeles, think they have found an effective system.

Writing in the Proceedings of the National Academy of Sciences, they describe attaching strands of polyethylene glycol (PEG) to neutral liposomes (lipid particles with the genes inside). The PEG increased the stability and duration of the liposomes in the bloodstream, and antibodies tethered to some of the PEG strands directed the liposomes to the blood-brain barrier transport system controlled by the transferrin receptor. Luciferase gene expression showed that the method succeeded in delivering the gene throughout the central nervous system, including neurons, choroid plexus epithelium and the brain's microvasculature.

Regarding the use of this system in humans, said Pardridge, "The practical tools to conduct brain gene therapy in humans already exist. We have genetically engineered antibodies for use in humans that should be 10 times more effective than in rats."—Hakon Heimer

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Primary Papers

  1. . Noninvasive gene targeting to the brain. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7567-72. PubMed.