BRISBANE, Calif., March 8, 2019 /PRNewswire/ --
Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a
genomic medicines company, announced today the publication in
Nature Communications of improvements to its zinc finger
nuclease (ZFN) platform technology, which yield a 64-fold increase
in the diversity of ZFNs available for targeting any DNA segment.
As demonstrated in the manuscript, this improved targeting
capability enables highly precise editing of chosen genomic loci.
ZFN technology is an engineerable gene editing platform that is
currently being evaluated in clinical trials for
Mucopolysaccharidosis Type I (MPS I), MPS II, hemophilia B, beta
thalassemia and sickle cell disease.
The manuscript, "Diversifying the Structure of Zinc Finger
Nucleases for High-Precision Genome Editing", describes protein
engineering work by Dr. David
Paschon and colleagues at Sangamo that has led to the
development of new ZFN architectures. The modifications include the
reversal of the order of the DNA binding and nuclease domains, as
well as the incorporation of new linkers that enable base skipping
between otherwise adjacent fingers within each ZFN.
"In developing nucleases for any therapeutic application, a
critical requirement is the ability to position the double-stranded
break for maximal clinical efficacy," said Ed Rebar, Ph.D., Sangamo's Chief Technology
Officer. "In many cases, this consideration restricts the optimal
cleavage target to a narrow sequence window, and for this reason,
increasing targeting precision has been a longstanding concern in
the field. The new architectures, which have substantially improved
our targeting capabilities, will help ensure that we can target the
optimal window for any therapeutic application. This speaks to the
versatility of our ZFN genome editing technology."
Sangamo researchers developed new linkers that attach the FokI
nuclease domain to the amino terminus of the DNA-binding zinc
finger array, as opposed to the carboxy terminal attachment used in
canonical ZFNs. This modification allows the design of nucleases in
which each ZFN of a dimer is able to recognize either DNA strand,
yielding three alternative ZFN dimer configurations, effectively
increasing the number of design options for any target sequence by
a factor of four. New linkers were also developed that allow
base-skipping between adjacent fingers within a zinc finger array.
These new linkers enable an engineered ZFN to bind alternative,
partially frame-shifted DNA sequences with new zinc finger designs
while maintaining the same cleavage site, thereby increasing the
number of design options by an additional factor of 16.
Incorporating both improvements into our ZFN platform resulted in
an overall 64-fold increase in the number of ZFN design options
available for efficient genome editing at any target cleavage
site.
The manuscript also highlights preclinical studies performed
using the new ZFN architectures, which demonstrate a high degree of
precision, efficiency, and specificity across three therapeutic
applications.
These modifications along with several other improvements have
been incorporated into Sangamo's second generation ZFN platform
technology.
About Sangamo
Sangamo Therapeutics, Inc. is focused on translating
ground-breaking science into genomic medicines with the potential
to transform patients' lives using the Company's platform
technologies in genome editing, gene therapy, gene regulation and cell therapy. For
more information about Sangamo, visit the Company's website
at www.sangamo.com.
Forward-Looking Statements
This press release may contain forward-looking statements based
on Sangamo's current expectations. These forward-looking statements
include, without limitation, the improved targeting capabilities
that enable highly precise editing of chosen genomic loci, improved
ZFN technology will result in greater clinical efficacy or safety
in clinical trials, the ability to target more diseases as a result
of the improvements, and the ability of the new ZFN architectures
to demonstrate a high degree of precision, efficiency and
specificity across three therapeutic applications. 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 our clinical trials, whether the
clinical trials will validate the safety and efficacy of our
product candidates, whether later stage studies or clinical trials
will validate the results from the preclinical studies on the new
ZFN architectures; and whether the new ZFN technology will result
in the opportunity to pursue new targets or improved safety or
efficacy in clinical trials; Sangamo's ability to develop
commercially viable products; and the potential for technological
developments by our competitors that will be better than our ZFN
technology. 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 for the year ended
December 31, 2018. Sangamo
Therapeutics, Inc. assumes no obligation to update the
forward-looking information contained in this press release.
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SOURCE Sangamo Therapeutics, Inc.