Scientists from The Whitehead Institute used zinc finger nucleases (ZFNs) designed by Sangamo BioSciences, Inc., to efficiently and precisely modify the genomes of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Human ESCs and iPSCs are useful tools in drug discovery and development. Scientists also hope to use these cells therapeutically in transplantation medicine and other regenerative applications. The research was described in a paper which appears in latest issue of the scientific journal Nature Biotechnology.

"The application of ZFN technology to human stem cells opens a new phase in human genetics," said Rudolf Jaenisch, M.D., a member of the Whitehead Institute and Professor of Biology at Massachusetts Institute of Technology (MIT). "In contrast to mouse stem cells which have been easy to modify, it has been very difficult and time-consuming to modify genes in human ESCs and iPSCs. This has severely limited their usefulness for the study of cell differentiation and as models for human disease. The work that our team published in Nature Biotechnology demonstrates that ZFNs enable new, rapid, efficient and specific methods to work with stem cells giving researchers the tools to gain valuable insights into how embryonic stem cells differentiate into adult cells and enabling the generation of patient-specific models of human disease."

Stem cells differ from other cell types in two fundamental ways. First, they are unspecialized cells capable of renewing themselves through cell division. Second, under certain conditions, they can be induced to become tissue- or organ-specific cells with special functions. Stem cells have the potential to develop into the body's many different cell types and in many tissues they serve a repair function, differentiating and replacing damaged cells. iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state. An advantage of iPSCs is that they can be derived from the adult cells of a person and will possess the same genetic background as that individual.

"These data are another powerful demonstration of the specificity and broad applicability of Sangamo's ZFP technology across medically and commercially relevant cell types," stated Philip Gregory, D. Phil., Sangamo's chief scientific officer and vice president of research. "The ability to efficiently modify stem cells enables the generation of valuable new tools for drug screening and the study of human disease as well as therapeutic applications in regenerative medicine."

In the article published, Dr. Jaenisch and his team demonstrated the broad applicability of gene editing applications enabled by ZFNs in hESCs and hiPSCs. In one example, they generated hESCs that carried a reporter gene. This gave researchers a visual method to clearly identify undifferentiated cells from those that had differentiated to their final cell type. In another example they inserted a new gene into a specific site in the genome of hESCs and demonstrated that ZFNs can be used to generate reporter cells in non-expressed genes in the genomes of hESCs and iPSCs, tools that will be useful in the study of cell fate and differentiation protocols.

Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification.