Using human pluripotent stem cells and DNA-cutting protein from meningitis bacteria, researchers from the Morgridge Institute for Research and Northwestern University have created an efficient way to target and repair defective genes.
Writing today (Monday, Aug. 12, 2013) in the Proceedings of the National Academy of Sciences, the team reports that the novel technique is much simpler than previous methods and establishes the groundwork for major advances in regenerative medicine, drug screening and biomedical research.
Zhonggang Hou of the Morgridge Institute’s regenerative biology team and Yan Zhang of Northwestern University served as first authors on the study; James Thomson, director of regenerative biology at the Morgridge Institute, and Erik Sontheimer, professor of molecular biosciences at Northwestern University, served as principal investigators.
“With this system, there is the potential to repair any genetic defect, including those responsible for some forms of breast cancer, Parkinson’s and other diseases,” Hou said. “The fact that it can be applied to human pluripotent stem cells opens the door for meaningful therapeutic applications.”
Zhang said the Northwestern University team focused on Neisseria meningitidis bacteria because it is a good source of the Cas9 protein needed for precisely cleaving damaged sections of DNA.
“We are able to guide this protein with different types of small RNA molecules, allowing us to carefully remove, replace or correct problem genes,” Zhang said. “This represents a step forward from other recent technologies built upon proteins such as zinc finger nucleases and TALENs.”
These previous gene correction methods required engineered proteins to help with the cutting. Hou said scientists can synthesize RNA for the new process in as little as one to three days – compared with the weeks or months needed to engineer suitable proteins.
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