Chem & Bio Engineering,
Год журнала:
2024,
Номер
2(3), С. 132 - 155
Опубликована: Дек. 23, 2024
Proteins
are
an
important
therapeutic
modality
in
modern
medicine.
However,
their
inherent
inability
to
traverse
cell
membranes
essentially
limits
application
extracellular
targets.
Recent
advances
intracellular
protein
delivery
have
enabled
access
traditionally
"undruggable"
targets
and
paved
the
way
precisely
modulate
cellular
functions.
This
Review
provides
a
comprehensive
examination
of
key
mechanisms
emerging
technologies
that
facilitate
transport
functional
proteins
across
membranes.
Delivery
methods
categorized
into
physical,
chemical,
biological
approaches,
each
with
distinct
advantages
limitations.
Physical
enable
direct
entry
but
often
pose
challenges
related
invasiveness
technical
complexity.
Chemical
strategies
offer
customizable
solutions
enhanced
control
over
targeting
uptake,
yet
may
face
issues
cytotoxicity
scalability.
Biological
approaches
leverage
naturally
occurring
processes
achieve
efficient
transport,
though
regulatory
production
consistency
remain
hurdles.
By
highlighting
recent
advancements,
challenges,
opportunities
within
approach,
this
review
underscores
potential
unlock
new
pathways
transform
drug
development
paradigms.
EBioMedicine,
Год журнала:
2024,
Номер
106, С. 105266 - 105266
Опубликована: Авг. 1, 2024
The
Chimeric
Antigen
Receptor
(CAR)
T
cell
therapy
has
emerged
as
a
ground-breaking
immunotherapeutic
approach
in
cancer
treatment.
To
overcome
the
complexity
and
high
manufacturing
cost
associated
with
current
ex
vivo
CAR
products,
alternative
strategies
to
produce
cells
directly
body
have
been
developed
recent
years.
These
involve
direct
infusion
of
genes
via
engineered
nanocarriers
or
viral
vectors
generate
situ.
This
review
offers
comprehensive
overview
advancements
development
cell-targeted
generation
Additionally,
it
identifies
challenges
method
potential
these
issues.
Macromolecular Bioscience,
Год журнала:
2024,
Номер
24(4)
Опубликована: Янв. 16, 2024
Abstract
Nucleic
acid‐based
therapies
are
seeing
a
spiralling
surge.
Stimuli‐responsive
polymers,
especially
pH‐responsive
ones,
gaining
widespread
attention
because
of
their
ability
to
efficiently
deliver
nucleic
acids.
These
polymers
can
be
synthesized
and
modified
according
target
requirements,
such
as
delivery
sites
the
nature
In
this
regard,
endosomal
escape
mechanism
polymer–nucleic
acid
complexes
(polyplexes)
remains
topic
considerable
interest
owing
various
plausible
mechanisms.
This
review
describes
current
progress
in
polyplexes
state‐of‐the‐art
chemical
designs
for
polymers.
The
importance
is
also
discussed
dissociation
constant
(i.e.,
p
K
)
designing
new
generation
along
with
assays
monitor
quantify
behavior.
Further,
use
machine
learning
addressed
prediction
polymer
design
find
novel
structures
pH
responsiveness.
will
facilitate
advanced
efficient
delivery.
Current Opinion in Chemical Biology,
Год журнала:
2024,
Номер
81, С. 102506 - 102506
Опубликована: Авг. 1, 2024
Despite
impressive
recent
establishment
of
therapeutic
nucleic
acids
as
drugs
and
vaccines,
their
broader
medical
use
is
impaired
by
modest
performance
in
intracellular
delivery.
Inefficient
endosomal
escape
presents
a
major
limitation
responsible
for
inadequate
cytosolic
cargo
release.
Depending
on
the
carrier,
this
barrier
can
strongly
limit
or
even
abolish
acid
Different
strategies
hypothesized
mechanisms
are
reviewed.
Molecular Therapy,
Год журнала:
2024,
Номер
32(3), С. 580 - 608
Опубликована: Янв. 29, 2024
Cardiovascular
disease
(CVD)
continues
to
impose
a
significant
global
health
burden,
necessitating
the
exploration
of
innovative
treatment
strategies.
Ribonucleic
acid
(RNA)-based
therapeutics
have
emerged
as
promising
avenue
address
complex
molecular
mechanisms
underlying
CVD
pathogenesis.
We
present
comprehensive
review
current
state
RNA
in
context
CVD,
focusing
on
diverse
modalities
that
bring
about
transient
or
permanent
modifications
by
targeting
different
stages
biology
central
dogma.
Considering
immense
potential
therapeutics,
we
identified
common
gene
targets
could
serve
interventions
for
prevalent
Mendelian
caused
single
mutations,
well
acquired
CVDs
developed
over
time
due
various
factors.
These
offer
opportunities
develop
RNA-based
treatments
tailored
specific
genetic
and
pathways,
presenting
novel
precise
approach
pathogenesis
both
types
cardiovascular
conditions.
Additionally,
discuss
challenges
associated
with
delivery
strategies
achieve
targeted
system.
This
highlights
combat
paving
way
future
advancements
therapeutics.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
Gene
delivery
systems
must
overcome
multiple
barriers,
with
endosomal
escape
representing
a
prominent
obstacle.
This
work
has
previously
shown
that
bacterial
phospholipase
C
(PLC)
enabled
of
non‐viral
protein‐based
DNA
system
termed
TFAMoplex.
Building
upon
this,
this
introduces
calcium‐responsive
designed
to
enhance
through
non‐covalent
capturing
PLC
the
TFAMoplex
followed
by
its
release
within
endosomes
and
nanobody‐mediated
targeting
membrane.
approach
leads
improved
TFAMoplexes
enabling
transfection
HeLa
cells
in
full
serum
half
maximal
effective
concentration
(EC
50
)
less
than
200
ng
per
mL
serum,
using
only
5
nM
PLC.
Particularly,
modular
capture,
could
potentially
be
adapted
other
agents
constrained
poor
escape.
These
findings
present
promising
strategy
achieve
efficient
escape,
offering
prospects
for
macromolecules,
particular
nucleic
acids.
Journal of Controlled Release,
Год журнала:
2024,
Номер
373, С. 252 - 264
Опубликована: Июль 18, 2024
In
an
earlier
investigation,
our
group
introduced
the
TFAMoplex,
a
transfection
agent
based
on
mitochondrial
transcription
factor
A
(TFAM)
protein,
which
complexes
DNA
into
nanoparticles.
The
original
TFAMoplex
further
contained
bacterial
phospholipase
to
achieve
endosomal
escape,
and
vaccinia-related
kinase
1
(VRK1),
significantly
boosted
efficiency
of
system
by
unknown
mechanism.
This
study
aims
at
replacing
VRK1
within
with
dynein
light
chain
proteins,
specifically
RP3,
directly
tether
motor
complex
for
enhanced
cytosolic
transport.
To
confirm
interaction
between
resulting
fusion
we
examined
binding
kinetics
TFAM-RP3
intermediate
chains
2.
Furthermore,
established
proteomics-based
assay
compare
protein
interactions
different
variants,
including
RP3-modified
version
VRK1-containing
system.
significant
shifts
interactors
were
observed,
especially
nucleolar
proteins.
Leveraging
this
knowledge,
incorporated
one
these
nuclear
leucine-rich
repeat-containing
59
(LRRC59),
in
improvement
properties
compared
comparable
levels
versus
original,
version.
not
only
advances
comprehension
but
also
offers
broader
insights
potential
engineering
designing
effective
gene
delivery
systems.
