ACS Nano,
Год журнала:
2024,
Номер
18(44), С. 30293 - 30306
Опубликована: Окт. 24, 2024
In
utero
gene
editing
with
mRNA-based
therapeutics
has
the
potential
to
revolutionize
treatment
of
neurodevelopmental
disorders.
However,
a
critical
bottleneck
in
clinical
application
been
lack
mRNA
delivery
vehicles
that
can
efficiently
transfect
cells
brain.
this
report,
we
demonstrate
intracerebroventricular
(ICV)
injection
densely
PEGylated
lipid
nanoparticles
(ADP-LNPs)
containing
an
acid-degradable
PEG–lipid
safely
and
effectively
deliver
for
enzymes
fetal
mouse
brain,
resulting
successful
transfection
brain
cells.
ADP-LNPs
Cre
transfected
30%
Ai9
mice
had
no
detectable
adverse
effects
on
development
postnatal
growth.
addition,
neural
stem
progenitor
mRNA,
which
subsequently
proliferated
caused
over
40%
cortical
neurons
60%
hippocampal
be
edited
treated
10
weeks
after
birth.
Furthermore,
using
Angelman
syndrome,
paradigmatic
disorder,
as
disease
model,
carrying
Cas9
gRNA
induced
indels
21%
within
7
days
postpartum,
underscoring
precision
approach.
These
findings
LNP/mRNA
complexes
have
transformative
tool
disorders
set
stage
frontier
treating
focuses
curing
genetic
diseases
before
Theoretical and Natural Science,
Год журнала:
2025,
Номер
82(1), С. 33 - 38
Опубликована: Янв. 15, 2025
CRISPI-Cas
9
technology
is
currently
the
most
popular
gene
editing
tool,
which
has
been
used
in
biomedical
research
and
clinical
treatment,
but
it
also
problem
of
off-target
effects
that
cause
unexpected
mutations,
limits
its
safety
efficacy.
Now,
various
machine
learning
models
have
trained
to
predict
events
order
to:
Gene
more
precise.
In
terms
both
accuracy
interpretability
there
are
still
issues
existing
models.
This
paper
focused
on
reviewing
Machine
archery
Off
Target
Prediction
their
performance.
The
results
this
study
show
deep
model
high
prediction
events,
provides
a
reference
for
optimization
strategies.
reveal
lot
room
development
improving
editing,
an
in-depth
sustainable
technology.
application
limitations,
including
inadequacy
applicability
multiple
contexts.
future
attention
can
be
paid
new
biological
indicators,
establishment
accurate
models,
improvement
with
explanatory
interpretation,
so
as
safely
apply
agricultural
treatment
improvement.
Molecular Pharmaceutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 29, 2025
Lipid
nanoparticles
(LNPs)
are
an
effective
delivery
system
for
gene
therapeutics.
By
optimizing
their
formulation,
the
physiochemical
properties
of
LNPs
can
be
tailored
to
improve
tissue
penetration,
cellular
uptake,
and
precise
targeting.
The
application
these
targeted
strategies
within
LNP
framework
ensures
efficient
therapeutic
agents
specific
organs
or
cell
types,
thereby
maximizing
efficacy.
In
realm
genome
editing,
have
emerged
as
a
potent
vehicle
delivering
CRISPR/Cas
components,
offering
significant
advantages
such
high
in
vivo
incorporation
machine
learning
into
optimization
platforms
therapeutics
represents
advancement,
harnessing
its
predictive
capabilities
substantially
accelerate
research
development
process.
This
review
highlights
dynamic
evolution
technology,
which
is
expected
drive
transformative
progress
field
therapy.
Molecular Therapy — Methods & Clinical Development,
Год журнала:
2025,
Номер
33(1), С. 101436 - 101436
Опубликована: Фев. 16, 2025
Lipid
nanoparticles
(LNPs)
are
now
highly
effective
transporters
of
nucleic
acids
to
the
liver.
This
liver-specificity
is
largely
due
their
association
with
certain
serum
proteins,
most
notably
apolipoprotein
E
(ApoE),
which
directs
them
liver
cells
by
binding
low-density
lipoprotein
(LDL)
receptors
on
hepatocytes.
The
liver's
distinct
anatomy,
its
various
specialized
cell
types,
also
influences
how
LNPs
taken
up
from
circulation,
cleared,
and
they
in
delivering
treatments.
In
this
review,
we
consider
factors
that
facilitate
LNP's
targeting
explore
latest
advances
liver-targeted
LNP
technologies.
Understanding
targeted
can
help
for
design
optimization
nanoparticle-based
therapies.
Comprehension
cellular
interaction
biodistribution
not
only
leads
better
treatments
diseases
but
delivers
insight
directing
other
tissues,
potentially
broadening
range
therapeutic
applications.
Cell Proliferation,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 27, 2025
ABSTRACT
Genetic
diseases
have
long
posed
significant
challenges,
with
limited
breakthroughs
in
treatment.
Recent
advances
gene
editing
technologies
offer
new
possibilities
therapy
for
the
treatment
of
inherited
disorders.
However,
traditional
methods
limitations
that
hinder
their
potential
clinical
use,
such
as
capabilities
and
production
unintended
byproducts.
To
overcome
these
limitations,
prime
(PE)
has
been
developed
a
powerful
tool
precise
efficient
genome
modification.
In
this
review,
we
provide
an
overview
latest
advancements
PE
its
applications
Furthermore,
examine
current
delivery
vehicles
employed
delivering
systems
vitro
vivo,
analyze
respective
benefits
limitations.
Ultimately,
discuss
challenges
need
to
be
addressed
fully
unlock
remission
or
cure
genetic
diseases.
Nucleic Acids Research,
Год журнала:
2025,
Номер
53(5)
Опубликована: Фев. 27, 2025
Effective
genome
editing
requires
a
sufficient
dose
of
CRISPR-Cas9
ribonucleoproteins
(RNPs)
to
enter
the
target
cell
while
minimizing
immune
responses,
off-target
editing,
and
cytotoxicity.
Clinical
use
Cas9
RNPs
currently
entails
electroporation
into
cells
ex
vivo,
but
no
systematic
comparison
this
method
packaged
RNP
delivery
has
been
made.
Here
we
compared
two
strategies,
enveloped
vehicles
(EDVs),
investigate
dosage
requirements
for
editing.
Using
fluorescence
correlation
spectroscopy,
determined
that
>1300
per
nucleus
are
typically
required
productive
EDV-mediated
was
>30-fold
more
efficient
than
electroporation,
occurs
at
least
2-fold
faster
EDV
comparable
total
doses.
We
hypothesize
differences
in
efficacy
between
these
methods
result
part
from
increased
duration
nuclear
residence
resulting
delivery.
Our
results
directly
compare
showing
could
dramatically
reduce
amount
experimental
or
clinical
Nanomaterials,
Год журнала:
2025,
Номер
15(7), С. 540 - 540
Опубликована: Апрель 2, 2025
Clustered
regularly
interspaced
short
palindromic
repeats/CRISPR-associated
protein
9
(CRISPR-Cas9),
an
emerging
gene-editing
technology,
has
recently
gained
rapidly
increasing
attention.
However,
the
lack
of
efficient
delivery
vectors
to
deliver
CRISPR-Cas9
specific
cells
or
tissues
hindered
translation
this
biotechnology
into
clinical
applications.
Chemically
synthesized
nanoparticles
(NPs),
as
attractive
non-viral
platforms
for
CRISPR-Cas9,
have
been
extensively
investigated
because
their
unique
characteristics,
such
controllable
size,
high
stability,
multi-functionality,
bio-responsive
behavior,
biocompatibility,
and
versatility
in
chemistry.
In
review,
key
considerations
precise
design
chemically
synthesized-based
include
encapsulation,
cellular
uptake,
targeting
cells,
endosomal
escape,
controlled
release.
We
discuss
cutting-edge
strategies
integrate
chemical
modifications
that
guide
genome-editing
machinery
edits.
also
highlighted
rationale
intelligent
nanoparticle
design.
particular,
we
summarized
promising
functional
groups
molecules
can
effectively
optimize
carrier
function.
addition,
review
focuses
on
advances
widespread
application
NPs
biomedical
fields
promote
development
safe,
specific,
delivering
systems,
providing
references
accelerating
translational
