Ribonucleic
acid
(RNA)
nanocarriers,
specifically
lipid
nanoparticles
and
polymeric
nanoparticles,
enable
RNA
transfection
both
in
vitro
vivo;
however,
only
a
small
percentage
of
endocytosed
by
cell
is
delivered
to
the
cytosolic
machinery,
minimizing
its
effect.
nanocarriers
face
two
major
obstacles
after
endocytosis:
endosomal
escape
release.
Overcoming
simultaneously
challenging
because
usually
achieved
using
high
positive
charge
disrupt
membrane.
However,
this
typically
also
inhibits
release
anionic
strongly
bound
nanocarrier
electrostatic
interactions.
Many
address
one
over
other
despite
growing
body
evidence
demonstrating
that
are
crucial
for
transfection.
In
review,
we
survey
various
strategies
have
been
employed
accomplish
with
focus
on
nanomaterials.
We
first
consider
requirements
must
achieve
delivery
including
protection
from
degradation,
cellular
internalization,
escape,
then
discuss
current
polymers
used
examine
achieving
Finally,
review
stimuli-responsive
While
continues
be
challenge
efficient
transfection,
many
new
innovations
materials
elucidated
promising
strategies.
Advanced Materials,
Год журнала:
2024,
Номер
36(31)
Опубликована: Июнь 6, 2024
Abstract
The
recent
success
of
gene
therapy
during
the
COVID‐19
pandemic
has
underscored
importance
effective
and
safe
delivery
systems.
Complementing
lipid‐based
systems,
polymers
present
a
promising
alternative
for
delivery.
Significant
advances
have
been
made
in
past,
with
multiple
clinical
trials
progressing
beyond
phase
I
several
companies
actively
working
on
polymeric
systems
which
provides
assurance
that
carriers
can
soon
achieve
translation.
massive
advantage
structural
tunability
vast
chemical
space
is
being
leveraged
to
mitigate
shortcomings
traditional
polycationic
improve
translatability
Tailored
approaches
diverse
nucleic
acids
specific
subcellular
targets
are
now
designed
therapeutic
efficacy.
This
review
describes
polymer
design
improved
by
polyplexes
covalent
polymer‐nucleic
acid
conjugates.
also
offers
brief
note
novel
computational
techniques
design.
concludes
an
overview
current
state
therapies
clinic
as
well
future
directions
their
translation
clinic.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
176, С. 116910 - 116910
Опубликована: Июнь 8, 2024
Therapeutic
proteins
provided
new
opportunities
for
patients
and
high
sales
volumes.
However,
they
are
formulated
extracellular
targets.
The
lipophilic
barrier
of
the
plasma
membrane
renders
vast
array
intracellular
targets
out
reach.
Peptide-based
delivery
systems,
namely
cell-penetrating
peptides
(CPPs),
have
few
safety
concerns,
low
immunogenicity,
with
control
over
administered
doses.
This
study
investigates
CPP-based
protein
systems
by
classifying
them
into
CPP-protein
"covalent
conjugation"
CPP:
"non-covalent
complexation"
categories.
Covalent
conjugates
ensure
proximity
CPP
to
cargo,
which
can
improve
cellular
uptake
endosomal
escape.
We
will
discuss
various
aspects
covalent
through
non-cleavable
(stable)
or
cleavable
bonds.
Non-cleavable
produced
recombinant
DNA
technology
express
complete
fusion
in
a
host
cell
chemical
ligation
protein,
ensures
stability
during
process.
bonds
classified
pH-sensitive
redox-sensitive
bonds,
enzyme-cleavable
physical
stimuli
linkers
(light
radiation,
ultrasonic
waves,
thermo-responsive).
highlighted
key
characteristics
non-covalent
complexes
electrostatic
hydrophobic
interactions
preserve
conformational
integrity
cargo.
CPP-mediated
complexation,
such
as
zippers,
adaptor
methods,
avidin-biotin
technology,
featured.
Conclusively,
complexation
methods
appropriate
when
number
samples
be
screened.
In
contrast,
biological
activity
is
critical
compartment,
conjugation
protocols
preferred.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(2), С. 578 - 578
Опубликована: Янв. 11, 2025
Most
rare
diseases
(RDs)
encompass
a
diverse
group
of
inherited
disorders
that
affect
millions
people
worldwide.
A
significant
proportion
these
are
driven
by
functional
haploinsufficiency,
which
is
caused
pathogenic
genetic
variants.
Currently,
most
treatments
for
RDs
limited
to
symptom
management,
emphasizing
the
need
therapies
directly
address
deficiencies.
Recent
advancements
in
gene
therapy,
particularly
with
adeno-associated
viruses
(AAVs)
and
lipid
nanoparticle-encapsulated
messenger
RNA
(mRNA),
have
introduced
promising
therapeutic
approaches.
AAV
vectors
offer
durable
expression,
extensive
tissue
tropism,
safety
profile
makes
them
leading
choice
delivery;
however,
limitations
remain,
including
packaging
size
immune
response.
In
contrast,
mRNA
therapeutics,
formulated
LNPs,
facilitate
transient
protein
expression
without
risk
genomic
integration,
supporting
repeated
dosing
pharmacokinetic
control,
though
less
long-term
than
AAVs.
This
review
analyzes
latest
developments
technologies
monogenic
disorders,
focusing
on
preclinical
clinical
outcomes,
vector
design,
delivery
challenges.
We
also
key
regulatory
immunological
considerations
impacting
success.
Together,
technology
underscore
new
era
RD
treatment,
providing
innovative
tools
target
root
expanding
approaches
patients
who
currently
face
medical
options.
Molecular Pharmaceutics,
Год журнала:
2024,
Номер
21(8), С. 3743 - 3763
Опубликована: Июль 2, 2024
The
coronavirus
(COVID-19)
pandemic
has
underscored
the
critical
role
of
mRNA-based
vaccines
as
powerful,
adaptable,
readily
manufacturable,
and
safe
methodologies
for
prophylaxis.
treatments
are
emerging
a
hopeful
avenue
plethora
conditions,
encompassing
infectious
diseases,
cancer,
autoimmune
genetic
rare
disorders.
Nonetheless,
in
vivo
delivery
mRNA
faces
challenges
due
to
its
instability,
suboptimal
delivery,
potential
triggering
undesired
immune
reactions.
In
this
context,
development
effective
drug
systems,
particularly
nanoparticles
(NPs),
is
paramount.
Tailored
with
biophysical
chemical
properties
susceptible
surface
customization,
these
NPs
have
demonstrated
enhanced
led
approval
several
NPs-based
formulations
clinical
use.
Despite
advancements,
necessity
developing
refined,
targeted
NP
system
remains
imperative.
This
review
comprehensively
surveys
biological,
translational,
progress
NPs-mediated
therapeutics
both
prevention
treatment
diverse
diseases.
By
addressing
factors
enhancing
existing
methodologies,
it
aims
inform
future
precise
efficacious
therapeutic
interventions.
ACS Pharmacology & Translational Science,
Год журнала:
2022,
Номер
6(1), С. 76 - 87
Опубликована: Дек. 7, 2022
Accumulating
evidence
indicates
that
oxidative
stress
and
inflammation
are
involved
in
the
physiopathology
of
liver
fibrogenesis.
Nuclear
factor
erythroid
2-related
2
(Nrf2)
is
a
key
transcription
factor,
which
regulates
expression
redox
regulators
to
establish
cellular
homeostasis.
The
Nrf2
modulator
can
serve
as
primary
defense
against
cytotoxic
effects
stress.
We
designed
chimeric
Keap1–Keap1
peptide
(KKP1)
based
on
proteolysis-targeting
chimera
technology.
KKP1
not
only
efficiently
penetrate
into
rat
hepatic
stellate
cell
line
(HSC-T6)
cells
but
also
induce
Keap1
protein
degradation
by
ubiquitination–proteasome
pathway,
releases
promotes
transcriptional
activity
Nrf2/antioxidant
response
element
pathway.
It
then
activates
downstream
antioxidant
factors,
glutamate-cysteine
ligase
catalytic
subunit
heme
oxygenase-1
(HO-1).
Finally,
inhibits
nuclear
factor-kappaB
inflammatory
signal
tumor
necrosis
alpha,
interleukin-1beta
further
fibrosis
biomarker
gene.
current
research
suggests
our
may
provide
new
avenue
for
future
treatment
fibrosis.
