Whitehead Institute - Founding Member

The recent demonstration of in vitro reprogramming using transduction of four transcription factors by Yamanaka and colleagues represents a major advance in the field. However, major questions regarding the mechanism of in vitro reprogramming need to be understood and will be one focus of the talk. A major impediment in realizing the potential of ES and iPS cells to study human diseases is the inefficiency of gene targeting. Methods based on Zn finger or TALEN mediated genome editing have allowed us to overcome the inefficiency of homologous recombination in human pluripotent cells. Using these genome editing approaches we have established efficient protocols to target expressed and silent genes in human ES and iPS cells. The most recent advance comes from the use of the CRISPR/ Cas9 system to engineer ES cells and mice. This technology allows the simultaneous editing of multiple genes and will facilitate establishing relevant models to study human disease.

We have used this technology to generate isogenic pairs of cells that differ exclusively at a disease causing mutation. The talk will describe the use of isogenic pairs of mutant and control iPS cells to establish in vitro systems for the study of diseases such as Parkinson’s and Rett syndrome.