Liposome-Mediated Gene Therapy for Brain Tumors

The first antibody allowed the liposomes to be transported across the blood-brain barrier in the mice, while the second antibody allowed the liposomes to specifically bind to the target human tumor cells. Expression plasmids encoding a short hairpin RNA directed at nucleotides 2529-2557 of human EGFR mRNA were encapsulated inside the liposomes.

The investigators worked with mice that had been inoculated with 500,000 human U87 glioma cancer cells. Results published in the June 1, 2004, issue of Clinical Cancer Research showed that the delivery of the RNAi expression plasmids resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation into new DNA or intracellular calcium signaling. Weekly RNAi gene therapy caused reduced tumor expression of EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer.

"This is the first drug delivery system that demonstrates that by using RNA interference technology, you can prolong life threatened by cancer,” said senior author Dr. William Pardridge, professor of medicine at the University of California, Los Angeles. "By solving the delivery problem, powerful molecular tools and therapies such as RNA interference can be moved to clinical trials where they can be tested to see how much benefit the patient gets.”