New DNA Editing Discovery Could Lead to Cure of Cystic Fibrosis, Sickle Cell Anaemia & Other Genetic Diseases

ImageResearchers at the Gladstone Institute of Cardiovascular Disease, San Francisco, California, have developed an innovative technique that can efficiently edit the human genetic code — one letter at a time, and which eventually could boost scientists’ ability to study — and ultimately cure — genetic diseases like cystic fibrosis and sickle cell anaemia. A report by Gladstone’s Anne D. Holden, PhD notes that sometimes simply a one-letter change in the human genetic code makes the difference between good health and these debilitating, and sometimes deadly afflictions. The Gladstone research team led by Principal Investigator Bruce Conklin, MD, describes in the latest issue of the journal Nature Methods how they have solved the problem of how to efficiently and accurately capture rare genetic mutations that cause disease, and potentially fix them. “Advances in human genetics have led to the discovery of hundreds of genetic changes linked to disease, but until now we’ve lacked an efficient means of studying them,” Dr. Holden cites Dr. Conklin commenting. “To meet this challenge, we must have the capability to engineer the human genome, one letter at a time, with tools that are efficient, robust and accurate. And the method that we outline in our study does just that.” The research paper, entitled “Isolation of single-base genome-edited human iPS cells without antibiotic selection” (published online before print 09 February 2014 Nature Methods (2014) doi:10.1038/nmeth.2840) is co-authored by Bruce R Conklin, Yuichiro Miyaoka, Amanda H Chan, Luke M Judge, Jennie Yoo, Miller Huang, Trieu D Nguyen, Paweena P Lizarraga, and Po-Lin So, variously of the Gladstone Institute of Cardiovascular Disease and several departments of University of California at San Francisco. The co-authors note that “precise editing of human genomes in pluripotent stem cells by homology-driven repair of targeted nuclease–induced cleavage has been hindered by the difficulty of isolating rare clones. We developed an efficient method to capture rare mutational events, enabling isolation of mutant lines with single-base substitutions without antibiotic selection. This method facilitates efficient induction or reversion of mutations associated with human disease in isogenic human induced pluripotent stem cells.” They observe that until recently, human genetics was primarily observational, but newly developed genome engineering tools now allow scientists to directly test the cellular consequences of discrete genetic changes. The Gladstone/UCSF team have developed efficient methods to edit one residue at a time in living human iPS cells, resulting in “isogenic” iPS cell lines that are identical except for a single alteration, and these isogenic iPS disease models are now yielding phenotypes that are helping to explain the molecular basis of several human diseases. They conclude that In the future safer and more effective drugs will be developed using genetically defined iPS-derived disease models. On his Gladstone Institute laboratory Web page, Dr. Conklin explains that Up until recently, human genetics was primarily observational, but that these newly developed genome engineering tools now allow them to directly test the cellular consequences of discrete genetic changes. The Conklin Lab researchers have developed efficient methods to edit one residue at a time in living human iPS cells, resulting in “isogenic” iPS cell lines that are identical except for a single alteration. These isogenic iPS disease models are now yielding phenotypes that are helping to explain the molecular basis of several human diseases.

Source: Bio News Texas

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