Nature Medicine,
Journal Year:
2023,
Volume and Issue:
29(2), P. 412 - 421
Published: Feb. 1, 2023
Abstract
Dominant
missense
pathogenic
variants
in
cardiac
myosin
heavy
chain
cause
hypertrophic
cardiomyopathy
(HCM),
a
currently
incurable
disorder
that
increases
risk
for
stroke,
heart
failure
and
sudden
death.
In
this
study,
we
assessed
two
different
genetic
therapies—an
adenine
base
editor
(ABE8e)
potent
Cas9
nuclease
delivered
by
AAV9—to
prevent
disease
mice
carrying
the
heterozygous
HCM
variant
R403Q.
One
dose
of
dual-AAV9
vectors,
each
one
half
RNA-guided
ABE8e,
corrected
≥70%
ventricular
cardiomyocytes
maintained
durable,
normal
structure
function.
An
additional
provided
more
editing
atria
but
also
increased
bystander
editing.
AAV9
delivery
effectively
inactivated
allele,
albeit
with
dose-dependent
toxicities,
necessitating
narrow
therapeutic
window
to
maintain
health.
These
preclinical
studies
demonstrate
considerable
potential
single-dose
therapies
correct
or
silence
development
HCM.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Jan. 16, 2023
Abstract
Clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)/CRISPR-associated
protein
9
(Cas9)
gene-editing
technology
is
the
ideal
tool
of
future
for
treating
diseases
by
permanently
correcting
deleterious
base
mutations
or
disrupting
disease-causing
genes
with
great
precision
and
efficiency.
A
variety
efficient
Cas9
variants
derivatives
have
been
developed
to
cope
complex
genomic
changes
that
occur
during
diseases.
However,
strategies
effectively
deliver
CRISPR
system
diseased
cells
in
vivo
are
currently
lacking,
nonviral
vectors
target
recognition
functions
may
be
focus
research.
Pathological
physiological
resulting
from
disease
onset
expected
serve
as
identifying
factors
targeted
delivery
targets
gene
editing.
Diseases
both
varied
complex,
choice
appropriate
methods
different
important.
Meanwhile,
there
still
many
potential
challenges
identified
when
targeting
CRISPR/Cas9
treatment.
This
paper
reviews
current
developments
three
aspects,
namely,
type,
vector,
characteristics.
Additionally,
this
summarizes
successful
examples
clinical
trials
finally
describes
possible
problems
associated
applications.
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(17), P. 6240 - 6240
Published: Aug. 28, 2020
Many
genetic
diseases
and
undesirable
traits
are
due
to
base-pair
alterations
in
genomic
DNA.
Base-editing,
the
newest
evolution
of
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)-Cas-based
technologies,
can
directly
install
point-mutations
cellular
DNA
without
inducing
a
double-strand
break
(DSB).
Two
classes
base-editors
have
been
described
thus
far,
cytosine
(CBEs)
adenine
(ABEs).
Recently,
prime-editing
(PE)
has
further
expanded
CRISPR-base-edit
toolkit
all
twelve
possible
transition
transversion
mutations,
as
well
small
insertion
or
deletion
mutations.
Safe
efficient
delivery
editing
systems
target
cells
is
one
most
paramount
challenging
components
for
therapeutic
success
BEs.
Due
its
broad
tropism,
well-studied
serotypes,
reduced
immunogenicity,
adeno-associated
vector
(AAV)
emerged
leading
platform
viral
genome
agents,
including
DNA-base-editors.
In
this
review,
we
describe
development
various
base-editors,
assess
their
technical
advantages
limitations,
discuss
potential
treat
debilitating
human
diseases.
Journal of Advanced Research,
Journal Year:
2020,
Volume and Issue:
29, P. 207 - 221
Published: Oct. 21, 2020
It
is
a
long-standing
goal
of
scientists
and
breeders
to
precisely
control
gene
for
studying
its
function
as
well
improving
crop
yield,
quality,
tolerance
various
environmental
stresses.
The
discovery
modification
CRISPR/Cas
system,
nature-occurred
editing
tool,
opens
an
era
precision
breeding.In
this
review,
we
first
introduce
the
brief
history
followed
mechanism
application
system
on
study
improvement.
Currently,
genome
has
been
becoming
mature
cutting-edge
biotechnological
tool
improvement
that
already
used
in
many
different
traits
crops,
including
pathogen
resistance,
abiotic
tolerance,
plant
development
morphology
even
secondary
metabolism
fiber
development.
Finally,
point
out
major
issues
associating
with
future
research
directions.Key
Scientific
Concepts
Review:
CRISPR/Cas9
robust
powerful
targeting
individual
DNA
RNA
sequence
genome.
can
be
target
knockin,
knockout
replacement
monitoring
regulating
expression
at
epigenome
levels
by
binding
specific
sequence.
Agrobacterium-mediated
method
still
efficient
delivering
regents
into
targeted
cells.
However,
other
delivery
methods,
such
virus-mediated
method,
have
developed
enhanced
potentials
CRISPR/Cas9-based
PAM
requirement
offers
CRISPR/Cas9-targted
genetic
loci
also
limits
CRISPR/Cas9.
Discovering
new
Cas
proteins
modifying
current
enzymes
play
important
role
editing.
Developing
better
methods
eliminating
off-target
effects,
finding
key/master
genes
controlling
growth
two
directions
