Tuesday June 15, 2004
Boston Cure Project
This is from the world of brain cancer, but it also has potential applications in other neurological diseases like MS. A research team from UCLA recently demonstrated in mice a technique for delivering shRNA molecules to brain tumor cells. shRNA molecules silence genes by binding to the mRNA expressed by these genes before proteins can be built from them. In this experiment, the researchers silenced the gene that encodes epidermal growth factor receptor (EGFR), which is involved in cell proliferation. Mice with brain tumors who received the treatment had survival times that were 88% longer than those of their untreated counterparts.
The significant development in this study was the delivery package engineered by the team to get the shRNA past the blood-brain barrier and into the tumor cells. The package is composed of a liposome (a fatty membrane) with two types of antibodies on its surface. One antibody recognizes and binds to transferrin, a protein on the blood-brain barrier. This binding allows the liposome to pass through the barrier. The other antibody binds to the human insulin receptor found on the surface of tumor cells; this permits entry into the cell itself where the shRNA is released to do its work.
Getting therapeutic agents past the blood-brain barrier is a notoriously
difficult task, so this development holds great potential for neurological
diseases. At this point we are just beginning to identify genes whose expression
may be harmful in MS (e.g., see last week's report of Nogo in inhibiting
neural regeneration in EAE), but once these are better understood it is
conceivable that RNA interference therapies will be beneficial for people
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