Sangamo BioSciences Announces Publication of First Demonstration of
Inactivation of Extra Chromosome Responsible for Down Syndrome
Nature Publication Demonstrates Specificity and Versatility of ZFP Technology
to Modify the Human Genome
RICHMOND, Calif., July 17, 2013
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.
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
"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.
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 www.sangamo.com.
ZFP Therapeutic^® is a registered trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements based on Sangamo's
current expectations. These forward-looking statements include, without
limitation, the potential of ZFNs to advance the studies and understanding of
Down syndrome and human chromosome inactivation, research and development of
novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP
technology platform. Actual results may differ materially from these
forward-looking statements due to a number of factors, including uncertainties
relating to the initiation and completion of stages of our clinical trials,
whether the clinical trials will validate and support the tolerability and
efficacy of ZFNs, technological challenges, Sangamo's ability to develop
commercially viable products and technological developments by our
competitors. For a more detailed discussion of these and other risks, please
see Sangamo's SEC filings, including the risk factors described in its Annual
Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo
assumes no obligation to update the forward-looking information contained in
this press release.
SOURCE Sangamo BioSciences, Inc.
Contact: Elizabeth Wolffe, Ph.D., Sangamo BioSciences, Inc., +1-510-970-6000
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