Sangamo BioSciences, Inc. (PRNewsFoto/Sangamo BioSciences, Inc.)

RICHMOND, Calif., July 17, 2013 /PRNewswire/ --Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the publication of groundbreaking research using zinc finger DNA-binding protein (ZFP) technology to insert a gene that permanently "silences" the extra copy of chromosome 21, which is the root cause of Down syndrome (DS). This advance, accomplished in induced pluripotent stem cells (iPSCs) derived from DS patients, provides a model to study the basic biology of DS which may enable the development of drugs that can potentially rebalance the cellular processes and pathologies that are impacted by this disorder.

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The work was led by the laboratory of Jeanne Lawrence, Ph.D., interim chair and professor of cell & developmental biology at the University of Massachusetts Medical School, in collaboration with Sangamo scientists and was published as an Advance Online Publication in Nature http://dx.doi.org/10.1038/nature12394.

"Until now our ability to correct cells carrying a chromosomal abnormality, by specifically silencing, or shutting down, expression of essentially all genes across a chromosome of our choosing was outside the realm of possibility," said Dr. Lawrence."However, this goal has been realized by using ZFNs to introduce, into a defined site in chromosome 21, a copy of a gene that normally functions to shut down the extra copy of the X chromosome in females.This provides a means to understand the cellular pathologies of DS, important for development of therapeutics, and also provides a needed model to study human chromosome inactivation."

Down syndrome, or Trisomy 21, is a genetic condition in which a person has a third copy of chromosome 21 giving them a total of forty-seven chromosomes instead of the usual forty-six. DS is the leading genetic cause of intellectual disabilities. Individuals with DS also have a higher risk for many conditions, including congenital heart defects, hematopoietic disorders, and early-onset Alzheimer's disease.

"The data further demonstrate the potential of ZFN-mediated genome editing to achieve unique biological outcomes which may have significant medical and therapeutic value," stated Philip Gregory, D. Phil., Sangamo's vice president, research and chief scientific officer. "In these studies, Sangamo's ZFN technology was used to insert a 17Kb DNA sequence containing a copy of the XIST gene into a pre-defined location in a particular chromosome. This is a substantially larger DNA sequence than is commonly used for genome editing and demonstrates the precision and efficiency of the ZFN-mediated process."

The paper entitled "Translating Dosage Compensation to Trisomy 21" described the highly specific and efficient ZFN-mediated insertion of copy of a large gene called XIST, into chromosome 21 in cultured iPSCs derived from DS patients. XIST encodes an RNA which normally functions in early development to shut down one of the two X chromosomes present in females, a process called dosage compensation. The XIST gene product functions by coating the chromosome from which it is expressed resulting in the silencing of the majority of the genes on that chromosome. In the study described by Jiang et al. in Nature, the silencing was observed on the extra, or third, copy of chromosome 21 in cells modified using the ZFNs. By comparing unmodified cells with cells in which the extra chromosome had been silenced by ZFN-mediate XIST addition, the authors showed that XIST helps correct defects in cell growth and neural differentiation found in DS-derived cells. The strategy can be used to help define the cellular and molecular changes underpinning DS and other trisomy disorders, as well as provide a model to study human chromosome inactivation.

About Sangamo

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 and Phase 1 /2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic for the treatment of HIV/AIDS. Sangamo's other therapeutic programs are focused on monogenic diseases, including hemophilia, Huntington's disease and hemoglobinopathies such as beta-thalassemia and sickle cell anemia. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification and ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo has entered into a strategic collaboration with Shire AG to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases and has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at http://www.sangamo.com.

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Sangamo BioSciences Announces Publication of First Demonstration of Inactivation of Extra Chromosome Responsible for ...

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