Sangamo BioSciences And Sigma-Aldrich Announce Nature Biotechnology Study Demonstrating Zinc Finger Technology For Modification Of Human Stem Cells
Application of ZFN Technology in Stem Cells has Potential to Yield High Value Research Reagents and Therapeutic Products
St. Louis and Richmond, CA - Sigma-Aldrich Corporation and Sangamo BioSciences, Inc. announced today the publication of data demonstrating the use of Sangamo's ZFP Nucleases (ZFNs) for "gene-editing" in human stem cells. This work represents a significant advance in the ability to specifically and efficiently modify the human genome in stem cells potentially enabling the efficient generation of stem cell lines for use as models of human disease for medical research and for drug testing. In addition to its use in the generation of valuable research reagents, the technology has potential in the therapeutic application of stem cells.
The work, which was carried out in the laboratory of Luigi Naldini, M.D., Ph.D. at the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy, in collaboration with Sangamo scientists, was published in Nature Biotechnology as an advance online publication.
"This is a significant advance for both research and the potential therapeutic use of stem cells," stated Dr. Naldini, a senior author of the study. "Stem cells are the body's natural resource for regeneration and repair and the ability to efficiently add a therapeutic gene into the genome of a cell at a predetermined location or to correct a mutated gene in a patient's stem cells may enable us to provide a long term solution for many genetic diseases. The powerful combination of our highly efficient delivery platform and Sangamo's ZFN technology made possible unprecedented gene modification efficiency in these therapeutically important cells".
The data published in the Nature Biotechnology paper demonstrate that ZFN-mediated gene modification can be used to correct both mutations in the IL-2R gamma gene, the defective gene in X-linked severe combined immunodeficiency (X-linked SCID), and to add a therapeutic gene to a pre-determined 'safe-harbor' site in the genome of both human hematopoietic stem cells and human embryonic stem (ES) cells. This putative 'safe-harbor site' was selected by the investigators for its capacity to allow efficient expression of the therapeutic gene and to tolerate an insertion event without adverse effects.
"These data open new avenues for experimental biology, biotechnology and medicine," said Philip Gregory, D.Phil., Sangamo's vice president of research. "This year's Nobel Prize for Medicine recognized the importance of gene targeting, or the site specific manipulation of the mouse genome, which has revolutionized biology and enabled the generation of mouse cell-lines and transgenic mouse models of human disease. However, until now and the development of our ZFN technology, genomes of other species such as humans and plants could not be efficiently modified in a site specific manner. Our ZFN technology enables the specific and targeted modification of any genome of potentially any species and may enable the development not only of potential therapeutics but also human cell lines and transgenic animals bedsides the mouse that may be valuable models of human disease for medical research and drug development."
"This publication represents ground-breaking research in the use of ZFNs and stem cells. Sigma's aim is to enable this kind of cutting-edge science by making innovative technologies available to scientists throughout the world," stated David Smoller, Ph.D., President of Sigma-Aldrich's Research Biotech Unit. "This work demonstrates the specificity and efficiency with which Sangamo's ZFN technology platform can be used to correct and add DNA sequences into the genomes of living cells and is further proof of its power and broad applicability. The ZFN technology has potential applications in the rapid generation of both modified stem cells and somatic cell lines that can be used at multiple stages of disease research and drug development. We expect to have ZFN research reagents similar those used in this publication available to all research scientists in the very near future."
SOURCE: Sangamo BioSciences, Inc.