The Opportunities and Challenges of Gene Therapy for Treatment of Inherited Forms of Vision and Hearing Loss
Human Gene Therapy,
Год журнала:
2023,
Номер
34(17-18), С. 808 - 820
Опубликована: Авг. 29, 2023
Inherited
forms
of
blindness
and
deafness
are
highly
prevalent
severe
conditions
that
significantly
impact
the
lives
millions
people
worldwide.
The
lack
therapeutic
options
for
these
poses
a
major
socioeconomic
burden.
Over
last
decades,
gene
therapy
has
proven
to
be
life
changing
treatment
hereditary
acquired
diseases,
extensive
preclinical
investigation
in
animal
models
both
retinal
inner
ear
disorders
highlighted
promising
translational
opportunities
too.
This
led
dozens
clinical
trials
investigating
efficiency
therapy-based
approaches,
with
some
products
successfully
reaching
phase
III
development
or
even
market
authorization.
However,
challenges
remain
use
therapy,
which
related
features
delivery
vehicles
currently
available
characteristics
targeted.
Therefore,
further
developments
platforms'
design,
including
exploitation
novel
technologies
such
as
genome
editing,
RNA-targeted
therapies,
optogenetics,
actively
ongoing,
driving
field
forward.
In
this
study,
we
review
ongoing
applications
achievements
inherited
well
being
pursued
overcome
current
limitations.
Язык: Английский
Deferoxamine protects cochlear hair cells and hair cell-like HEI-OC1 cells against tert-butyl hydroperoxide-induced ototoxicity
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease,
Год журнала:
2024,
Номер
1870(3), С. 167024 - 167024
Опубликована: Янв. 17, 2024
Язык: Английский
The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs)
BMC Molecular and Cell Biology,
Год журнала:
2025,
Номер
26(1)
Опубликована: Янв. 20, 2025
Abstract
Background
Bioengineering
of
human
teeth
for
replacement
is
an
appealing
regenerative
approach
in
the
era
gene
therapy.
Developmentally
regulated
transcription
factors
hold
promise
quest
because
these
transcriptional
regulators
constitute
regulatory
networks
driving
cell
fate
determination.
Atonal
homolog
1
(Atoh1)
a
factor
basic
helix-loop-helix
(bHLH)
family
essential
neurogenesis
cerebellum,
auditory
hair
differentiation,
and
intestinal
stem
specification.
The
functional
versatility
Atoh1
prompted
us
to
test
possibility
that
may
intersect
dental
pulp
(DPSC)
network
governing
odontogenic
differentiation.
Methods
We
isolated
DPSCs
from
pulps
treated
cells
with
replication-deficient
adenoviral
vector
achieve
robust
ectopic
expression
Atoh1,
following
which
growth
differentiation
profiles
were
characterized.
Results
harboring
exhibited
approximately
3,000-fold
increase
compared
negative
control,
leading
increased
DPSC
proliferation
medium
(
P
<
0.05).
In
medium,
caused
early
induction
BMP2
0.001)
followed
by
late
BMP7
0.01)
Wnt
signaling
0.01).
BMP/Wnt
led
up
8-fold
master
osteogenic
Osterix
0.005)
while
exhibiting
no
significant
effect
on
Runx2
or
Dlx5,
are
abundantly
expressed
DPSCs.
stimulated
type
I
collagen
small
integrin-binding
ligand,
N-linked
glycoproteins
(SIBLINGs)
such
as
bone
sialoprotein
0.001),
dentin
matrix
protein
0.05),
sialophosphoprotein
0.005),
osteopontin
resulting
mineralization
phenotype
associated
metabolic
remodeling
marked
enhanced
glycolytic
flux
attenuated
mitochondrial
enzyme
activities.
Conclusions
despite
being
proneural
development,
possesses
novel
function
upon
This
vitro
study
demonstrates
mechanism
mediated
finding
offer
innovative
strategy
gene-based
regeneration
pulp-dentin
complex.
Язык: Английский
Enhancing hair regeneration: Recent progress in tailoring nano-structured lipid carriers through surface modification strategies
ADMET & DMPK,
Год журнала:
2024,
Номер
12(3), С. 431 - 462
Опубликована: Июль 20, 2024
Background
and
purpose:
Hair
loss
is
a
prevalent
problem
affecting
millions
of
people
worldwide,
necessitating
innovative
efficient
regrowth
approaches.
Nanostructured
lipid
carriers
(NLCs)
have
become
hopeful
option
for
transporting
bioactive
substances
to
hair
follicles
because
their
compatibility
with
the
body
capability
improve
drug
absorption.
Review
approach:
Recently,
surface
modification
techniques
been
used
enhance
regeneration
by
improving
customization
NLCs.
These
involve
applying
polymers,
incorporating
targeting
molecules,
modifying
charge.
Key
results:
The
conversation
focuses
on
how
these
stability,
body,
precise
delivery
within
Moreover,
it
explains
surface-modified
NLCs
can
bioavailability
growth-promoting
agents
like
minoxidil
finasteride.
Furthermore,
information
interact
given,
uncovering
possible
uses
in
treating
conditions.
Conclusion:
This
review
discusses
potential
altering
customize
them
enhanced
growth.
It
offers
important
upcoming
studies
Язык: Английский
Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome, and Transcriptome in Health and Disease
Biomolecules,
Год журнала:
2023,
Номер
13(10), С. 1534 - 1534
Опубликована: Окт. 17, 2023
Advanced
genomics,
transcriptomics,
and
epigenomics
techniques
are
providing
unprecedented
insights
into
the
understanding
of
molecular
underpinnings
central
nervous
system,
including
neuro-sensory
cochlea
inner
ear.
Here,
we
report
for
first
time
a
comprehensive
updated
overview
most
advanced
omics
study
nucleic
acids
their
applications
in
cochlear
research.
We
describe
available
vitro
vivo
models
hearing
research
principles
epigenomics,
alongside
technologies
(like
single-cell
spatial
omics),
which
allow
investigation
events
that
occur
at
resolution
while
retaining
information.
Язык: Английский
Atoh1 overexpression promotes Guinea pig bone marrow mesenchymal stem cells to differentiate into neural stem cell
Heliyon,
Год журнала:
2024,
Номер
10(12), С. e32952 - e32952
Опубликована: Июнь 1, 2024
Sensorineural
hearing
loss
(SNHL)
is
a
prevalent
condition
in
otolaryngology.
A
key
obstacle
finding
effective
strategies
for
regenerating
damaged
cochlear
hair
cells
adult
animals.
practical
and
reliable
approach
has
been
developed
to
create
superior
cell
source
stem
transplantation
the
inner
ear
treat
SNHL.
Atoh1
involved
differentiation
of
neurons,
intestinal
secretory
cells,
mechanoreceptors
including
auditory
thus
plays
an
important
role
neurogenesis.
Lentivirus-mediated
transfection
bone
marrow
mesenchymal
(BMSCs)
was
utilized
achieve
stable
expression
essential
transcription
factor
Atoh1,
which
crucial
developing
without
compromising
survival.
By
manipulating
induction
conditions
through
altering
growth
environment
using
anti-adherent
culture,
synergistic
impact
basic
fibroblast
(bFGF)
epidermal
(EGF)
effectively
applied
significantly
improve
efficiency
marrow-derived
(BMSC)
into
neural
(NSCs)
following
transfection,
thereby
reducing
time.
The
study
indicated
that
newly
proposed
transdifferentiation
method
transformed
BMSCs
NSCs
controlled
environment,
presenting
potential
promote
regeneration.
Язык: Английский
Future Perspectives in Idiopathic Sudden Sensorineural Hearing Loss
Опубликована: Янв. 1, 2024
Язык: Английский
The Proneural Transcription Factor Atoh1 Promotes Odontogenic/Osteogenic Differentiation in Human Dental Pulp Stem Cells (DPSCs)
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 5, 2024
Abstract
Background
Developmentally
regulated
transcription
factors
constitute
the
gene
regulatory
networks
driving
cell
fate
determination.
Atonal
homolog
1
(Atoh1)
is
a
factor
of
basic
helix-loop-helix
(bHLH)
family
essential
for
neurogenesis
in
cerebellum,
auditory
hair
differentiation,
and
intestinal
stem
specification.
The
functional
versatility
Atoh1
prompted
us
to
test
possibility
that
may
intersect
dental
pulp
(DPSC)
network
governing
odontogenic/osteogenic
differentiation.
DPSCs
were
isolated
from
human
pulps
amplified
culture.
treated
with
replication-deficient
adenoviral
vector
achieve
robust
expression
Atoh1,
following
which
cells
maintained
growth
or
osteogenic
medium.
Cell
proliferation
was
analyzed
by
MTT
assay.
Quantitative
polymerase
chain
reaction
(qPCR)
performed
measure
expression.
L-Lactate
spent
medium
quantified
assess
glycolytic
flux.
Enzyme
assays
carried
out
evaluate
glycolysis
mitochondrial
energy
metabolism.
Alizarin
Red
staining
used
matrix
mineralization.
Statistical
significance
set
at
P
<
0.05.
Results
harboring
exhibited
an
over
3,000-fold
increase
compared
negative
control,
leading
increased
DPSC
(P
0.05).
In
medium,
induced
BMP2
Wnt
signaling,
accompanied
up
8-fold
master
Osterix
0.005)
while
exhibiting
no
effect
on
Runx2.
stimulated
type
I
collagen
0.005),
bone
sialoprotein
0.001),
dentin
protein
0.05),
sialophosphoprotein
Osteopontin
resulting
mineralization
phenotype
associated
metabolic
remodeling
marked
enhanced
flux
attenuated
activities.
Conclusions
despite
being
proneural
development,
possesses
novel
function
upon
ectopic
DPSCs.
This
vitro
study
demonstrates
mechanism
mediated
finding
offer
innovative
strategy
regeneration
pulp-dentin
complex.
Язык: Английский
REGENERATIVE WEAKNESS OF THE INNER EAR AND BIOENGINEERED HEARING RESTORATION: A BRIEF PROBLEM OVERVIEW
OTORHINOLARYNGOLOGY,
Год журнала:
2023,
Номер
unknown, С. 91 - 100
Опубликована: Янв. 1, 2023
The
structure
of
the
hearing
organ
combines
simplicity
and
depth,
remaining
in
many
issues
subject
active
scientific
research.
ontogenesis
this
exquisite
mechanism
is
regulated
by
complex
still
incompletely
understood
mechanisms.
technological
tools
modern
biomedical
science
allow
not
only
to
study,
but
also
work
at
cellular
molecular
level.
In
article,
we
review
data
on
realism
restoring
population
human
auditory
receptors
promising
ways
solve
problem.
addition,
offer
an
answer
a
fundamental
question
–
why,
with
small
number
relatively
simply
arranged
receptor
cells
inner
ear,
their
self-restored.
Key
words:
spiral
organ,
stem
cells,
progenitors,
impairments,
regeneration,
bioprosthetics,
bioengineering.
Язык: Английский