bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 9, 2023
Abstract
Among
the
genome-editing
methods
for
repairing
disease-causing
mutations
resulting
in
dominant
inhibition,
homology-independent
targeted
integration
(HITI)-mediated
gene
insertion
of
normal
form
causative
is
useful
because
it
allows
development
mutation-agnostic
therapeutic
products.
For
rapid
optimization
and
validation
highly
effective
HITI-treatment
constructs
against
dominant-negative
inheritance
inherited
retinal
dystrophy,
we
improved
available
both
plasmid
adeno-associated
virus
(AAV)
vectors,
established
a
workflow
that
uses
vivo
electroporation
to
verify
efficacy.
By
targeting
mouse
Rhodopsin
gene,
derived
construct
which
HITI-mediated
occurs
80%-90%
transduced
rod
photoreceptor
cells.
This
suppressed
degeneration
induced
visual
restoration
mutant
mice.
The
rhodopsin
were
shown
be
AAV
this
construction
Peripherin
2
gene.
These
findings
suggest
reported
here
may
generation
various
target
genes
therapy
Frontiers in Genome Editing,
Год журнала:
2023,
Номер
5
Опубликована: Фев. 8, 2023
Clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
genome
editing
platform
heralds
a
new
era
of
gene
therapy.
Innovative
treatments
for
life-threatening
monogenic
diseases
the
blood
and
immune
system
are
transitioning
from
semi-random
addition
to
precise
modification
defective
genes.
As
these
therapies
enter
first-in-human
clinical
trials,
their
long-term
safety
efficacy
will
inform
future
generation
editing-based
medicine.
Here
we
discuss
significance
Inborn
Errors
Immunity
as
disease
prototypes
establishing
advancing
precision
We
review
feasibility
clustered
repeats-based
platforms
modify
DNA
sequence
primary
cells
describe
two
emerging
approaches
treat
RAG2
deficiency,
immunodeficiency,
FOXP3
regulatory
disorder.
Biology,
Год журнала:
2024,
Номер
13(10), С. 802 - 802
Опубликована: Окт. 8, 2024
Inner
ear
disorders,
including
sensorineural
hearing
loss,
Meniere’s
disease,
and
vestibular
neuritis,
are
prevalent
conditions
that
significantly
impact
the
quality
of
life.
Despite
their
high
incidence,
underlying
pathophysiology
these
disorders
remains
elusive,
current
treatment
options
often
inadequate.
Emerging
evidence
suggests
pericytes,
a
type
vascular
mural
cell
specialized
to
maintain
integrity
function
microvasculature,
may
play
crucial
role
in
development
progression
inner
disorders.
The
pericytes
present
microvasculature
both
cochlea
system,
where
they
regulate
blood
flow,
blood–labyrinth
barrier,
facilitate
angiogenesis,
provide
trophic
support
neurons.
Understanding
valuable
insights
into
lead
novel
diagnostic
therapeutic
strategies,
improving
standard
living.
This
comprehensive
review
aims
detailed
overview
highlighting
anatomy
physiology
analyzing
mechanisms
contribute
Furthermore,
we
explore
potential
pericyte-targeted
therapies,
antioxidant,
anti-inflammatory,
angiogenic
approaches,
as
well
gene
therapy
strategies.
The
endothelium
has
multiple
functions
from
maintaining
vascular
homeostasis,
providing
nutrition
and
oxygen
to
tissues,
evocating
inflammation,
under
adverse
conditions,
determining
endo-thelial
barrier
disruption
resulting
in
dysfunction.
Endothelial
dysfunction
represents
the
typical
condition
associated
with
pathogenesis
of
all
diseases
cardiovascular
system,
as
well
other
human
body’s
systems,
also
including
sepsis,
acute
respiratory
distress
syn-drome
COVID-19
distress.
Such
evidence
is
leading
identifying
potential
bi-omarkers
therapeutic
targets
for
preserving,
reverting,
or
restoring
integrity
functionality
by
early
treating
its
Here,
it
stresses
some
strategies
achieving
these
goals,
even
if
diverse
challenges
exist
require
a
significant
bench
work
an
in-creased
number
clinical
studies.
Current Gene Therapy,
Год журнала:
2024,
Номер
24(3), С. 208 - 216
Опубликована: Янв. 4, 2024
Abstract:
Hearing
loss
is
a
prevalent
sensory
impairment
significantly
affecting
communication
and
quality
of
life.
Traditional
approaches
for
hearing
restoration,
such
as
cochlear
implants,
have
limitations
in
frequency
resolution
spatial
selectivity.
Optogenetics,
an
emerging
field
utilizing
light-sensitive
proteins,
offers
promising
avenue
addressing
these
revolutionizing
rehabilitation.
This
review
explores
the
methods
introducing
Channelrhodopsin-
2
(ChR2),
key
protein,
into
cells
to
enable
optogenetic
stimulation.
Viral-
mediated
gene
delivery
widely
employed
technique
optogenetics.
Selecting
suitable
viral
vector,
adeno-associated
viruses
(AAV),
crucial
efficient
cells.
The
ChR2
inserted
vector
through
molecular
cloning
techniques,
resulting
introduced
via
direct
injection
or
round
window
membrane
delivery.
allows
expression
subsequent
light
sensitivity
targeted
Alternatively,
cell
transfection
non-viral
approach
cloned
plasmid
which
then
combined
with
agents
like
liposomes
nanoparticles.
mixture
applied
cells,
facilitating
entry
DNA
target
enabling
expression.
Optogenetic
stimulation
using
precise
selective
activation
specific
neurons
response
light,
potentially
overcoming
current
auditory
prostheses.
Moreover,
optogenetics
has
broader
implications
understanding
neural
circuits
involved
processing
behavior.
combination
techniques
provides
improving
restoration
strategies,
offering
potential
enhanced
resolution,
selectivity,
improved
perception.
Expert Review of Molecular Diagnostics,
Год журнала:
2024,
Номер
24(9), С. 753 - 765
Опубликована: Авг. 28, 2024
Sensorineural
hearing
impairment
(SNHI),
a
common
childhood
disorder
with
heterogeneous
genetic
causes,
can
lead
to
delayed
language
development
and
psychosocial
problems.
Next-generation
sequencing
(NGS)
offers
high-throughput
screening
high-sensitivity
detection
of
etiologies
SNHI,
enabling
clinicians
make
informed
medical
decisions,
provide
tailored
treatments,
improve
prognostic
outcomes.
Investigative Ophthalmology & Visual Science,
Год журнала:
2024,
Номер
65(13), С. 38 - 38
Опубликована: Ноя. 18, 2024
Purpose:
Among
the
genome-editing
methods
for
repairing
disease-causing
mutations
resulting
in
autosomal
dominant
retinitis
pigmentosa,
homology-independent
targeted
integration
(HITI)-mediated
gene
insertion
of
normal
form
causative
is
useful
because
it
allows
development
mutation-agnostic
therapeutic
products.
In
this
study,
we
aimed
rapid
optimization
and
validation
HITI-treatment
constructs
approach
developing
various
target
genes
mouse
models
retinal
degeneration.
Methods:
We
constructed
Cas9-driven
HITI
cassettes
plasmid
vectors
to
treat
Rho
gene.
A
workflow
utilizing
vivo
electroporation
was
established
validate
efficacy
these
constructs.
Single-cell
genotyping
conducted
evaluate
allelic
donor
insertion.
The
potency
adeno-associated
virus
(AAV)
examined
by
section
immunohistochemistry
optomotor
response
(OMR)
Rho+/P23H
mutant
mice.
also
Prph2
examine
workflow.
Results:
optimized
achieved
80%
90%
transduced
rod
photoreceptor
cells.
This
construct
effectively
suppressed
degeneration
induced
visual
restoration
Rhodopsin
demonstrated
AAV
are
adaptable
locus.
Conclusions:
study
showcases
a
highly
effective
against
dominant-negative
inheritance
inherited
dystrophy.
These
findings
suggest
potential
utility
genes,
advancing
therapy
products
diverse
genetic
disorders.
