'Think of fibronectin as Velcro'
Research breakthrough to affect efficiency of gene therapy

Related Link: IU Medical Center

By Ellen Gullett

A major breakthrough in improving the efficiency of gene therapy was reported this summer in an issue of "Nature Medicine."

Researchers from the Howard Hughes Medical Institute at the IU Medical Center and Takara Shuzo Co., Ltd., a leading biotechnology company in Japan that owns the worldwide patents for clone fibronectin fragments, propose that their findings have significant implications for future human gene therapy trials.

The research team reported that the human protein fibronectin, which already was known to have adhesion properties, also can act as an adhesive for retroviral particles that are used to transport genes into cells in gene therapy protocols.

David Williams, M.D., principal investigator of the study and member of the Herman B Wells Center for Pediatric Research at the IU Medical Center and a Howard Hughes Medical Institute investigator explains:

"In essence, think of fibronectin as Velcro and retroviral particles and stem cells as balls. Envision that, like Velcro, the fibronectin allows attachment of the retroviral particles and stem cells, or balls, immediately adjacent to each other. This then permits genes to pass easily from the retroviral ball to the stem cell ball."

Williams also said that the findings answer some of the unknown questions that have eluded gene therapy researchers and therefore allowed only slow, limited progress in this area of research. He noted that the findings have significant implications for gene therapy trials, and may have implications for the development of new strategies in treatment of retroviral infections such as HIV.

In gene transfer, retroviral particles are used to carry normal genes into cells of the body in order to correct defective genes. Gene therapy trials have had limited success, in part because of low gene transfer efficiency. Earlier research has shown that fibronectin is abundant in bone marrow and is responsible in part for the adherence in bone marrow of hematopoietic stem cells, the source of all other blood cells. This new research showed that retroviral particles also bind to the same area of fibronectin.

Williams and other researchers at the Medical Center are awaiting approval from the FDA to begin the first human gene therapy trial using this new technology in the treatment of children and adults with brain cancers.

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