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Dual Gene Therapy Suppresses Lung Cancer in Preclinical Test

small cell lung cancer by 70 to 80 percent 48 hours after treatment while leaving a control group of normal cells unaffected. The cancer cell lines treated with the gene combination had 2 to 3 times more cells killed by apoptosis than either gene nanoparticle had individually. The research team then confirmed these findings in the mouse studies.

The nanoparticle delivery system, which the researchers have used for years, consists of a plasmid gene expression cassette loaded with DNA that encodes either the p53 or the FUS1 protein. This is wrapped tightly in a form of cholesterol to protect it from the body's defense mechanisms. 'You can't deliver naked DNA for cancer therapy,' Ji says.

The nanoparticles accumulate mainly in the lungs, particularly in the tumors, Ji says. The positively charged nanoparticles are delivered to the negatively charged cancer cell membrane and taken into the cell, where the genes repeatedly express either p53 or FUS1 tumor-suppressing proteins.

Roth expects the research team to advance combination therapies to clinical trials in the coming years, either of genes or of genes with other biologic or chemotherapy agents.

'We certainly hope this approach will be more effective but we also think it's likely to be much less toxic, with fewer side effects, than other types of combined cancer therapy,' Roth says. 'These genes don't have much effect on normal tissue or normal cells when they are overexpressed. It's really just cancer cells where they seem to have their effect. Ultimately, the usefulness of this approach has to be proven in clinical trials.'

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