Thursday, July 14, 2011

Whitehead researchers fix mutated stem cells

By Rodney H. Brown

The Whitehead Institute at MIT has moved personalized medicine and gene therapy forward with the announcement of a technique that can correct disease-causing mutations in stem cells.

According to a release from MIT, researcher Frank Soldner and collaborators will publish a paper in the July 22 issue of the magazine Cell that describes two methods for either inserting or removing mutations that can cause early-onset Parkinson’s disease. While the main goal of the work was to insert such mutations so that potential drugs can be tested against a single genome – with both the non-mutated control cells and the mutated test cells identical in all other aspects – one of the potential benefits is as a therapeutic.

The researchers used two proteins – zinc finger nucleases (ZFNs) and transcription activator like effector nucleases (TALENs) – to alter the genes in both human embryonic stem cells and induced pluripotent stem cells (cells taken from adults and made to function as stem cells). According to the release from MIT, the TALENs proteins work more quickly and are less expensive than the ZFNs proteins. In fact, the difference in time and cost is so great that researcher Dirk Hockemeyer said, “This opens up a lot of possibilities of what we will be able do because the generation of TALENs are so much faster and easier than that of ZFNs. It solves many of the issues that were holding us back.”

The theoretical therapeutic application would go like this: Cells are harvested from a patient suffering from a genetic-mutation-based disease and turned into induced pluripotent stem cells. The TALENS protein would then be applied and the mutation in the gene would be corrected. The non-mutation-bearing stem cells would then be reinjected into the patient and eventually supplant the disease-causing mutation-bearing cells, eliminating the underlying genetic cause of the condition.

The research was funded by grants from the National Institutes of Health and a Collaborative Innovation Award from the Howard Hughes Medical Institute.

Last month, Mary Gehring of the Whitehead Institute for Biomedical Research at MIT was named a 2011 Pew Scholar in Biomedical Science for epigenetics and genomics. The honor brings with it $240,000 over four years from Pew Charitable Trusts.