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Sangamo BioSciences Announces Publication of First Demonstration of Inactivation of Extra Chromosome Responsible for Down Syndrome
Date:7/17/2013

etic 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
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SOURCE Sangamo BioSciences, Inc.
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