Intellia Therapeutics’ Preclinical Data Show Continued Progress in In Vivo Gene Editing With Systemic Lipid Nanoparticle De...
August 18 2016 - 9:37PM
Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome
editing company focused on the development of potentially curative
therapeutics using CRISPR/Cas9 technology, presented preclinical
data demonstrating in vivo gene editing using lipid nanoparticles
(LNPs) to deliver CRISPR/Cas9. These data were presented at the
2016 meeting on Genome Engineering: The CRISPR/Cas Revolution, in
Cold Spring Harbor, New York.
In several in vitro and in vivo preclinical studies, the data
demonstrated:
- Editing efficiency in mouse liver of up to approximately 60
percent at the transthyretin (TTR) target site after a single
intravenous administration, consistently across different lobes.
This resulted in an associated decrease in serum TTR protein levels
of up to approximately 80 percent;
- Dose-dependent editing by LNP delivery;
- Undetectable Cas9 mRNA and guide RNA (gRNA) in the liver at 72
hours post administration;
- Repair patterns in mouse liver cells in vivo being best
predicted by primary mouse liver cells in vitro.
“Intellia has shown robust data that demonstrates the clinical
potential of the LNP delivery of CRISPR components. With a single
administration, we show significant editing at the target gene and
a related decrease in target protein in serum,” said David
Morrissey, Ph.D., Chief Technology Officer, Intellia Therapeutics.
“These early data also show that LNP delivery can lead to rapid
clearance of the Cas9 and guide components from the liver, an
important consideration for future clinical studies. Intellia
continues to make further advances, and we would expect greater
editing efficiency with continued optimization.”
Study Background
The preclinical editing studies were designed to explore the use
of lipid nanoparticles for delivery of CRISPR/Cas9 components to
the liver in mice and to mediate editing of target DNA within
hepatocytes. In general, for the LNPs in the studies, Cas9 mRNA was
co-formulated with chemically synthesized gRNAs targeting the mouse
TTR gene, and administered via one or two intravenous tail vein
injections. Additional studies were performed to evaluate the
impact on editing of variables including guide format, dosing
regimen and dose escalation.
About Intellia Therapeutics
Intellia Therapeutics is a leading genome editing company,
focused on the development of proprietary, potentially curative
therapeutics using the CRISPR/Cas9 system. Intellia believes the
CRISPR/Cas9 technology has the potential to transform medicine by
permanently editing disease-associated genes in the human body with
a single treatment course. Our combination of deep scientific,
technical and clinical development experience, along with our
leading intellectual property portfolio, puts us in a unique
position to unlock broad therapeutic applications of the
CRISPR/Cas9 technology and create a new class of therapeutic
products. Learn more about Intellia Therapeutics and CRISPR/Cas9 at
intelliatx.com; Follow us on Twitter @intelliatweets.
Forward-Looking StatementsThis press release
contains “forward-looking statements” within the meaning of the
Private Securities Litigation Reform Act of 1995. These forward
looking statements include, but are not limited to, statements
regarding our ability to advance CRISPR/Cas9 into therapeutic
products for severe and life-threatening diseases; the potential
timing and advancement of our clinical trials; the impact of our
collaborations with Novartis and Regeneron on our development
programs; the potential indications we may pursue, including our
sentinel indications; the potential timing of regulatory filings
regarding our development programs; and potential commercialization
opportunities for product candidates. Any forward-looking
statements in this press release are based on management's current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements. These risks and uncertainties
include, but are not limited to, the risk that any one or more of
our product candidates will not be successfully developed and
commercialized, the risk of cessation or delay of any of the
ongoing or planned clinical trials and/or our development of our
product candidates, the risk that the results of previously
conducted studies involving similar product candidates will not be
repeated or observed in ongoing or future studies involving current
product candidates, the risk that our collaboration
with Novartis or Regeneron will not continue or will not
be successful, and risks related to our ability to protect and
maintain our intellectual property position. For a discussion of
other risks and uncertainties, and other important factors, any of
which could cause our actual results to differ from those contained
in the forward-looking statements, see the section entitled "Risk
Factors" in our most recent quarterly report on Form 10-Q filed
with the Securities and Exchange Commission, as well as discussions
of potential risks, uncertainties, and other important factors in
our subsequent filings with the Securities and Exchange
Commission. All information in this press release is as of the
date of the release, and Intellia Therapeutics undertakes no duty
to update this information unless required by law.
Study Abstract
ROBUST IN VIVO GENE EDITING IN MOUSE HEPATOCYTES WITH SYSTEMIC
LIPID NANOPARTICLE DELIVERY OF CRISPR/CAS9 COMPONENTS
Jonathan D Finn, Mihir Patel, Amy Rhoden Smith, Lucinda Shaw,
Madeleine Youniss, Corey Ciullo, Reynald Lescarbeau, Jessica
Seitzer, Jacqueline Growe, Christian Dombrowski, Walter R Strapps,
Thomas M Barnes, David V Morrissey
Intellia Therapeutics, Cambridge, MA
There is considerable interest in the therapeutic potential of
CRISPR/Cas9-mediated gene editing to treat a wide variety of
genetic diseases; however, clinically viable delivery of
CRISPR/Cas9 components presents an obvious challenge. Effective and
safe delivery of CRISPR/Cas9 components, whether based on viral or
non-viral delivery vehicles, would require specific targeting of a
tissue or cell type; and brief half-life in order to minimize
potential off-target activity and innate and humoral immune
responses. In addition, the ability to re-administer the therapy to
attain stable, therapeutically relevant levels of gene editing
would be an advantage. With these requirements in mind, we have
explored the use of lipid nanoparticles (LNPs) for delivery of
CRISPR/Cas9 components to the liver to mediate editing of target
DNA within hepatocytes. Cas9 mRNA and chemically synthesized gRNA
specific to the mouse transthyretin gene (TTR) were co-formulated
into LNPs, and administered to mice via intravenous tail vein
injection. Various parameters were explored, including the nature
of the guide RNA (sgRNA vs. dgRNA & chemical modification), the
dosing regimen, and molecular strategy (single target site vs.
two-target site micro-deletion). We found that the best results
were obtained with a chemically modified single guide co-formulated
with Cas9 mRNA. We were able to achieve a median dose-dependent
editing of up to 55% of the gene copies in liver biopsies. A
corresponding dose-dependent reduction of serum transthyretin
protein levels was seen, with a decrease of up to 80%. The levels
of editing across liver lobes were in general highly consistent.
Notably, the DNA repair patterns in liver were distinctly different
from those seen in cell lines using the same TTR-specific gRNA.
These results demonstrate that therapeutically meaningful levels of
in vivo CRISPR/Cas9-mediated gene editing can be obtained with a
completely synthetic and scalable single-agent system, and suggest
that the treatment of liver-based genetic disease with CRISPR/Cas9
will be clinically viable.
Media Contact:
Jennifer Mound Smoter
Chief External Affairs & Communications Officer
+1 224-804-4462
jenn.smoter@intelliatx.com
Investor Contacts:
John Graziano
Trout Group
+1 646-378-2942
jgraziano@troutgroup.com
Chad Rubin
Trout Group
+1 646-378-2947
crubin@troutgroup.com
Intellia Therapeutics (NASDAQ:NTLA)
Historical Stock Chart
From Aug 2024 to Sep 2024
Intellia Therapeutics (NASDAQ:NTLA)
Historical Stock Chart
From Sep 2023 to Sep 2024