Protein Tags To Chase Down Tumors

CHEMOTHERAPY DELIVERS A powerful punch to some tumors, but it can damage the patient's organs and weaken the immune system. That's why doctors long for a magic bullet that would target only the tumor. They've tried anchoring drugs to antibodies that home in on specific sites. But these tend to be large molecules that don't penetrate tumors easily.

In the Mar. 28 issue of Nature, scientists at the Burnham Institute in La Jolla, Calif., describe a new method for generating small protein "tags" that can find their own way to specified "addresses" in the human body. Institute President Erkki Ruoslahti, a molecular biologist, and colleague Renata Pasqualini generate randomly shaped protein structures on the outer coating of billions of viruses. Injected into mice, the altered viruses bind to cells whose receptors match their protein structures. Scientists then remove the target organs--here, the brain and kidney--grind them up, and isolate viruses bound there.

In the case described in Nature, researchers found just three types of altered viruses in the brain and one type in the kidney. Their conclusion: These viruses contained the right protein tag required to bind with cells in those two organs. The researchers then cloned and cultured the viruses and isolated the DNA that generates the desired protein structures. The protein tags can be coupled with drugs or genes for delivery to the appropriate organ, says Ruoslahti. His lab is using the method to find tags for blood vessels that nourish tumors.

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