RICHMOND, Calif., Feb. 13, 2018 /PRNewswire/ --
Sangamo Therapeutics (Nasdaq: SGMO) yesterday presented preclinical
data demonstrating the Company's engineering capabilities in T cell
genome editing using zinc finger nucleases (ZFNs). Sangamo
Scientist Sumiti Jain, Ph.D.
delivered the presentation, "Dual Knock-Out of Endogenous T-Cell
Receptor and Human Leukocyte Antigen and Site-Specific Insertion of
a CD19-CAR: Implications for Allogeneic T Cell Therapy," at the
Keystone Symposium on Emerging Cellular Therapies: T Cells and
Beyond.
Sangamo's T cell engineering capabilities have advanced rapidly
in the last two years with recent improvements to the architecture
of zinc finger nucleases (ZFNs). These novel architectural
enhancements have resulted in a 300-fold increase in potential
design options for a given genetic sequence, yielding higher
on-target modification activity, with editing efficiencies now
reaching as high as 99.5%, and off-target cleavage consistently
below the level of detection.
"For T cell editing applications in oncology, the improvements
to our ZFN platform technology across the dimensions of precision,
efficiency and specificity open a wealth of potential product
opportunities in autologous and allogeneic cellular therapies,"
said Dr. Sandy Macrae, CEO of
Sangamo.
At the Keystone Symposium, Dr. Jain's presentation highlighted
Sangamo's ability to accomplish highly efficient "multiplex" genome
editing of T cells. Efficient multiplex editing, the ability to
make multiple genetic changes in a single step, is critical for the
development of next-generation cellular immunotherapies to treat
liquid and solid tumors in cancer, as well as in other areas such
as autoimmune disorders and infectious diseases. Multiplex editing
enables simultaneous "knock out" of certain genes to prevent the
body from rejecting the treatment and "knock in" of new genes to
equip the modified T cells with targeted antitumor functions.
"With more than a decade of experience in ex vivo genome
editing, we have developed a deep understanding of T cell
immunology that enables us to optimize the T cell editing process,"
said Dr. Gary Lee, Senior Director
of Genome Editing at Sangamo. "The improved ZFN platform provides
an extremely potent editing platform that allows us to use
significantly reduced doses of mRNA and AAV. As a result, the gene
editing process is highly efficient and well tolerated during ex
vivo cell expansion, and, we believe, is the 'manufacturing
ready' profile needed for clinical product development."
At the Keystone Symposium, Jain presented work leading to a T
cell with four edits achieved in a single step:
- Elimination of endogenous T cell receptor (TCR) expression by
knock-out of the TCR alpha constant locus (TRAC) with greater than
97% efficiency
- Elimination of (human leukocyte antigen) HLA Class I proteins
by knock-out of b2-microglobulin (B2M) with greater than
91% efficiency
- Targeted integration into either the TRAC or B2M locus with
double knock-out of TCR and HLA Class I:
-
- 91% efficiency with green fluorescent protein (GFP)
- 77% efficiency with CD19 chimeric antigen receptor (CAR)
- Four simultaneous edits including triple knockout of TCR (93%),
B2M (96%), CISH, a checkpoint gene (93%), and targeted insertion of
GFP (91%) resulting in 76% of all cells with all four edits
Sangamo's strategy in oncology is to advance the T cell editing
platform in collaboration with partners that have synergistic
technologies and with the appropriate development and
commercialization expertise.
Dr. Jain's slides are available on the Presentations +
Publications page of the technology section of Sangamo's
website.
About Sangamo's Zinc Finger Nucleases
Sangamo's
proprietary genome editing technology is based on a naturally
occurring class of proteins called zinc finger DNA-binding proteins
(ZFPs) which recognize and bind to specific sequences of DNA.
Sangamo can engineer these naturally occurring ZFPs to bind to
virtually any chosen DNA sequence. By combining ZFPs with nucleases
(DNA cutting enzymes) to create zinc finger nucleases (ZFNs),
Sangamo can harness the powerful targeting capabilities of zinc
fingers to edit the human genome, specifically knocking out a DNA
sequence or adding a new gene in a precise location.
In 2017, Sangamo scientists have reported on recent advancements
in design and engineering which have enhanced the profile of ZFNs
across three important criteria for the development of therapeutic
genome editing: Precision, Efficiency and Specificity. With
thousands of zinc finger modules in the Sangamo library and an
array of linkers attaching the zinc fingers and the FOK1 nuclease
domain, Sangamo is able to assemble highly specific ZFN pairs for
virtually any chosen target site. For any given 20-base pair window
in the genome, Sangamo has on average 450 functionally distinct ZFN
modules to evaluate. Sangamo believes that the very high design
density of the Company's ZFN library has operational advantages in
choosing a final ZFN pair with an optimal profile to advance into
potential clinical development.
About Sangamo Therapeutics
Sangamo Therapeutics, Inc.
is focused on translating ground-breaking science into genomic
therapies that transform patients' lives using the Company's
industry leading platform technologies in genome editing, gene
therapy, gene regulation and cell therapy. For more information
about Sangamo, visit www.sangamo.com.
Forward-Looking Statements
This press release
contains forward-looking statements, including, but not limited to,
statements related to Sangamo's expectations for cellular
immuno-oncology treatments, the clinical and therapeutic potential
of Sangamo's ZFN gene editing platform, Sangamo's strategy to
advance its T cell editing platform in collaboration with partners,
and other statements that are not historical facts. These
forward-looking statements are based on Sangamo's current plans,
objectives, estimates, expectations and intentions and inherently
involve significant risks and uncertainties. Actual results and the
timing of events could differ materially from those anticipated in
such forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks and
uncertainties associated with: gene therapy product candidate
development and the inherent uncertainty of clinical success,
including the risks that Sangamo and/or its collaborators may
encounter unanticipated toxicity or adverse events or fail to
demonstrate efficacy in clinical development; the initiation,
enrollment and completion of the stages of its clinical trials;
technological challenges; technological developments by its
competitors and others in the gene therapy and/or cellular
immuno-oncology treatment fields; Sangamo's dependence on
collaborations to further the development of its technology
platforms, including Sangamo's potential inability to successfully
enter into new collaborations with third parties on acceptable
terms, or at all, in order to advance its T cell editing platform.
A more detailed discussion of these and other risks and
uncertainties may be found under the caption "Risk Factors" and
elsewhere in Sangamo's SEC filings and reports, including Sangamo's
Quarterly Report on Form 10-Q for the quarter ended September 30, 2017 and future filings and reports
by Sangamo. Sangamo assumes no obligation to update the
forward-looking information contained in this press release.
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SOURCE Sangamo Therapeutics, Inc.