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RNA-Based Therapy Brings Hope for ‘Incurable’ Blood Cancer

Early research targets protein responsible for mantle cell lymphoma (Oct. 10)

According to an October 10 announcement from researchers at Tel Aviv University, one of the characteristics that define mantle cell lymphoma (MCL), a form of blood cancer, is heightened activity in the gene CCND1, which leads to over-production of cyclin D1, a protein that controls the proliferation of cells. In MCL, cyclin D1 production spins out of control, producing a 3,000- to 5,000-fold increase.

Now, scientists in the university’s Department of Cell Research and Immunology have developed a new class of drugs based on RNA interference that can repair or destroy faulty proteins and reprogram cells to act in normal ways. The new drugs have the ability to kill mutated cyclin D1 proteins and stop the over-proliferation of cells.

The team’s findings were published in the journal PLoS One.

In MCL, cyclin D1 is the exclusive cause of the over-production of B lymphocytes, which are responsible for generating antibodies. This makes the protein a perfect target for RNA interference, the researchers said. Because normal, healthy cells don't express the CCND1 gene, therapies that destroy the gene will attack only cancer cells. The RNA interference that the researchers have developed targets faulty cyclin D1 within cancerous cells. When the cells are inhibited from proliferating, they sense they are being targeted and begin to self-destruct.

In the laboratory, the researchers have successfully used their RNA interference in human cells — a crucial step towards proving that cyclin D1 can be targeted through the right interventions.

The researchers are working to develop a mouse population with MCL to test their newly developed therapies in vivo. Typically, new treatments for any disease are tested on human cells as well as in mouse models before being taken to clinical trials in humans. But there has never been a test using mice with this disease, the researchers said. The animal test will allow investigators to conduct a more cautious and in-depth investigation of this new class of drugs before moving to the clinical stage.

To deliver the new therapy into the body, the researchers plan to use nano-sized medical "submarines," which are designed to travel to the source of a disease and to offload drugs inside specific cells or proteins, as needed.

For more information, visit the Tel Aviv University Web site.

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