Pharmaceutics,
Год журнала:
2024,
Номер
16(6), С. 710 - 710
Опубликована: Май 24, 2024
Huntington’s
disease
(HD)
is
a
monogenic
neurodegenerative
disorder
caused
by
cytosine–adenine–guanine
(CAG)
trinucleotide
repeat
expansion
in
the
HTT
gene.
There
are
no
cures
for
HD,
but
genetic
basis
of
this
makes
gene
therapy
viable
approach.
Adeno-associated
virus
(AAV)-miRNA-based
therapies
have
been
demonstrated
to
be
effective
lowering
mRNA;
however,
blood–brain
barrier
(BBB)
poses
significant
challenge
delivery
brain.
Delivery
strategies
include
direct
injections
into
central
nervous
system,
which
invasive
and
can
result
poor
diffusion
viral
particles
through
brain
parenchyma.
Focused
ultrasound
(FUS)
an
alternative
approach
that
used
non-invasively
deliver
AAVs
temporarily
disrupting
BBB.
Here,
we
investigate
FUS-mediated
single-stranded
AAV9
bearing
cDNA
GFP
2-month-old
wild-type
mice
zQ175
HD
mouse
model
at
2-,
6-,
12-months.
FUS
treatment
improved
all
groups.
The
efficacy
was
similar
WT
groups,
with
exception
12-month
cohort,
where
observed
decreased
expression.
Astrocytosis
did
not
increase
after
treatment,
even
within
group
exhibiting
higher
baseline
levels
GFAP
These
findings
demonstrate
AAV9-based
targeted
regions
disease.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 7333 - 7333
Опубликована: Июль 4, 2024
Clustered
regularly
interspersed
short
palindromic
repeats
(CRISPR)/CRISPR-associated
protein
9
(Cas9)
technology
has
revolutionized
the
field
of
gene
therapy
as
it
enabled
precise
genome
editing
with
unprecedented
accuracy
and
efficiency,
paving
way
for
clinical
applications
to
treat
otherwise
incurable
genetic
disorders.
Typically,
requires
delivery
multiple
components
target
cells
that,
depending
on
platform
used,
may
include
messenger
RNA
(mRNA),
complexes,
DNA
fragments.
For
purposes,
these
have
be
efficiently
delivered
into
transplantable
cells,
such
primary
T
lymphocytes
or
hematopoietic
stem
progenitor
that
are
typically
sensitive
exogenous
substances.
This
challenge
limited
broad
applicability
those
strategies
which
efficient
methods
available.
Electroporation-based
methodologies
been
generally
applied
applications,
but
procedure-associated
toxicity
represented
a
major
burden.
With
advent
novel
less
disruptive
deliver
cargo
is
now
possible
safely
editing,
thus
expanding
strategies.
In
this
review,
we
describe
different
systems
available
components,
including
viral
non-viral
systems,
highlighting
their
advantages,
limitations,
recent
applications.
Recent
improvements
achieve
cell
specificity
represent
critical
development
enable
in
vivo
targeting
future
will
certainly
play
pivotal
role
field.
Advanced Drug Delivery Reviews,
Год журнала:
2024,
Номер
208, С. 115274 - 115274
Опубликована: Март 6, 2024
Ultrasound
enhances
drug
delivery
into
the
central
nervous
system
(CNS)
by
opening
barriers
between
blood
and
CNS
triggering
release
of
drugs
from
carriers.
A
key
challenge
in
translating
setups
vitro
to
vivo
settings
is
achieving
equivalent
acoustic
energy
delivery.
Multiple
devices
have
now
been
demonstrated
focus
ultrasound
brain,
with
concepts
emerging
also
target
spinal
cord.
Clinical
trials
date
used
facilitate
blood–brain
barrier.
While
most
focused
on
feasibility
safety
considerations,
therapeutic
benefits
are
beginning
emerge.
To
advance
translation
these
technologies
for
applications,
researchers
should
standardise
exposure
protocol
fine-tune
parameters.
Computational
modelling
be
increasingly
as
a
core
component
develop
both
delivering
accurate
reproducible
CNS.
This
field
holds
promise
transformative
advancements
management
pharmacological
treatment
complex
challenging
disorders.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(26)
Опубликована: Июнь 17, 2024
Advancing
our
understanding
of
brain
function
and
developing
treatments
for
neurological
diseases
hinge
on
the
ability
to
modulate
neuronal
groups
in
specific
areas
without
invasive
techniques.
Here,
we
introduce
Airy-beam
holographic
sonogenetics
(AhSonogenetics)
as
an
implant-free,
cell
type–specific,
spatially
precise,
flexible
neuromodulation
approach
freely
moving
mice.
AhSonogenetics
utilizes
wearable
ultrasound
devices
manufactured
using
3D-printed
metasurfaces.
These
are
designed
manipulate
neurons
genetically
engineered
express
ultrasound-sensitive
ion
channels,
enabling
precise
modulation
populations.
By
dynamically
steering
focus
Airy
beams
through
frequency
tuning,
is
capable
modulating
populations
within
subregions
striatum.
One
notable
feature
its
flexibly
stimulate
either
left
or
right
striatum
a
single
mouse.
This
flexibility
achieved
by
simply
switching
acoustic
metasurface
device,
eliminating
need
multiple
implants
interventions.
AhSonogentocs
also
integrates
seamlessly
with
vivo
calcium
recording
via
fiber
photometry,
showcasing
compatibility
optical
modalities
cross
talk.
Moreover,
can
generate
double
foci
bilateral
stimulation
alleviate
motor
deficits
Parkinson’s
disease
advancement
significant
since
many
disorders,
including
disease,
involve
dysfunction
regions.
type–specific
procedures,
provides
powerful
tool
investigating
intact
neural
circuits
offers
promising
interventions
disorders.
Advanced Drug Delivery Reviews,
Год журнала:
2024,
Номер
211, С. 115363 - 115363
Опубликована: Июнь 19, 2024
Adeno-associated
virus
(AAV)
vectors
have
emerged
as
a
promising
tool
in
the
development
of
gene
therapies
for
various
neurological
diseases,
including
Alzheimer's
disease
and
Parkinson's
disease.
However,
blood–brain
barrier
(BBB)
poses
significant
challenge
to
successfully
delivering
AAV
brain.
Strategies
that
can
overcome
BBB
improve
delivery
efficiency
brain
are
essential
successful
brain-targeted
therapy.
This
review
provides
an
overview
existing
strategies
employed
brain,
direct
intraparenchymal
injection,
intra-cerebral
spinal
fluid
intranasal
delivery,
intravenous
injection
BBB-permeable
AAVs.
Focused
ultrasound
has
technology
noninvasive
spatially
targeted
administered
by
injection.
also
summarizes
each
strategy's
current
preclinical
clinical
applications
treating
diseases.
Moreover,
this
includes
detailed
discussion
recent
advances
emerging
focused
ultrasound-mediated
delivery.
Understanding
state-of-the-art
these
approaches
is
critical
future
fulfill
great
promise
treatment.
