Nucleic Acid Therapeutics,
Год журнала:
2023,
Номер
33(3), С. 178 - 192
Опубликована: Апрель 24, 2023
Nucleic
acids
drugs
have
been
proven
in
the
clinic
as
a
powerful
modality
to
treat
inherited
and
acquired
diseases.
However,
key
challenges
including
drug
stability,
renal
clearance,
cellular
uptake,
movement
across
biological
barriers
(foremost
blood-brain
barrier)
limit
translation
clinical
efficacy
of
nucleic
acid-based
therapies,
both
systemically
central
nervous
system.
In
this
study
we
provide
an
overview
emerging
class
acid
therapeutic,
called
DNAzymes.
particular,
review
use
chemical
modifications
carrier
molecules
for
stabilization
and/or
delivery
DNAzymes
cell
animal
models.
Although
focuses
on
DNAzymes,
strategies
described
are
broadly
applicable
most
technologies.
This
should
serve
general
guide
selecting
improve
therapeutic
performance
ACS Nano,
Год журнала:
2021,
Номер
15(9), С. 13993 - 14021
Опубликована: Сен. 10, 2021
Oligonucleotides
(ONs)
comprise
a
rapidly
growing
class
of
therapeutics.
In
recent
years,
the
list
FDA-approved
ON
therapies
has
expanded.
ONs
are
small
(15-30
bp)
nucleotide-based
therapeutics
which
capable
targeting
DNA
and
RNA
as
well
other
biomolecules.
can
be
subdivided
into
several
classes
based
on
their
chemical
modifications
mechanisms
target
interactions.
Historically,
largest
hindrance
to
widespread
usage
been
inability
effectively
internalize
cells
escape
from
endosomes
reach
molecular
targets
in
cytosol
or
nucleus.
While
cell
uptake
improved,
"endosomal
escape"
remains
significant
problem.
There
range
approaches
overcome
this,
this
review,
we
focus
three:
altering
structure
ONs,
formulating
synthetic,
lipid-based
nanoparticles
encapsulate
biologically
loading
extracellular
vesicles.
This
review
provides
background
design
mode
action
existing
ONs.
It
presents
most
common
classifications
fundamental
scientific
perspective
roadmap
cellular
pathways
by
trafficked.
Finally,
delves
each
above-mentioned
delivery,
highlighting
principles
behind
covering
advances.
Frontiers in Oncology,
Год журнала:
2022,
Номер
12
Опубликована: Март 22, 2022
The
complexity
of
the
tumor
microenvironment
presents
significant
challenges
to
cancer
therapy,
while
providing
opportunities
for
targeted
drug
delivery.
Using
characteristic
signals
microenvironment,
various
stimuli-responsive
delivery
systems
can
be
constructed
sites.
Among
these,
pH
is
frequently
utilized,
owing
being
lower
than
that
blood
and
healthy
tissues.
pH-responsive
polymer
carriers
improve
efficiency
in
vivo
,
allow
delivery,
reduce
adverse
reactions,
enabling
multifunctional
personalized
treatment.
polymers
have
gained
increasing
interest
due
their
advantageous
properties
potential
applicability
therapy.
In
this
review,
recent
advances
in,
common
applications
of,
nanomaterials
therapy
are
summarized,
with
a
focus
on
different
types
polymers.
Moreover,
future
field
prospected.
Communications Medicine,
Год журнала:
2024,
Номер
4(1)
Опубликована: Янв. 5, 2024
Abstract
Antisense
oligonucleotides
(ASOs)
are
incredibly
versatile
molecules
that
can
be
designed
to
specifically
target
and
modify
RNA
transcripts
slow
down
or
halt
rare
genetic
disease
progression.
They
offer
the
potential
groups
of
patients
tailored
for
individual
cases.
Nonetheless,
not
all
variants
disorders
amenable
ASO-based
treatments,
hence,
it
is
important
consider
several
factors
before
embarking
on
drug
development
journey.
Here,
we
discuss
which
have
benefit
from
a
specific
type
ASO
approach,
based
pathophysiology
pathogenic
variant
type,
as
well
those
might
suitable
therapies.
We
further
explore
additional
aspects,
such
tissues,
intervention
time
points,
clinical
benefits,
need
considered
developing
compound.
Overall,
provide
an
overview
current
potentials
limitations
therapeutics
treatment
monogenic
disorders.
Nucleic Acid Therapeutics,
Год журнала:
2024,
Номер
34(2), С. 52 - 72
Опубликована: Март 20, 2024
Nucleic
acid-based
therapies
have
become
the
third
major
drug
class
after
small
molecules
and
antibodies.
The
role
of
nucleic
has
been
strengthened
by
recent
regulatory
approvals
tremendous
clinical
success.
In
this
review,
we
look
at
obstacles
that
hindered
field,
historical
milestones
achieved,
what
is
yet
to
be
resolved
anticipated
soon.
This
review
provides
a
view
key
innovations
are
expanding
acid
capabilities,
setting
stage
for
future
therapeutics.
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Авг. 5, 2024
Targeting
non-coding
RNAs
(ncRNAs),
including
microRNAs
(miRNAs)
and
long
(lncRNAs),
has
recently
emerged
as
a
promising
strategy
for
treating
malignancies
other
diseases.
In
recent
years,
the
development
of
ncRNA-based
therapeutics
targeting
protein-coding
genes
also
gained
momentum.
This
review
systematically
examines
ongoing
completed
clinical
trials
to
provide
comprehensive
overview
emerging
landscape
therapeutics.
Significant
efforts
have
been
made
advance
ncRNA
early
studies.
The
most
advanced
conducted
with
small
interfering
(siRNAs),
miRNA
replacement
using
nanovector-entrapped
mimics,
or
silencing
by
antisense
oligonucleotides.
While
siRNA-based
already
received
FDA
approval,
inhibitors,
lncRNA-based
are
still
under
evaluation
in
preclinical
We
critically
discuss
rationale
methodologies
strategies
illustrate
this
rapidly
evolving
field.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(4), С. 533 - 533
Опубликована: Апрель 20, 2024
The
TGF-β
family
is
a
group
of
25
kDa
secretory
cytokines,
in
mammals
consisting
three
dimeric
isoforms
(TGF-βs
1,
2,
and
3),
each
encoded
on
separate
gene
with
unique
regulatory
elements.
Each
isoform
plays
unique,
diverse,
pivotal
roles
cell
growth,
survival,
immune
response,
differentiation.
However,
many
researchers
the
field
often
mistakenly
assume
uniform
functionality
among
all
isoforms.
Although
TGF-βs
are
essential
for
normal
development
cellular
physiological
processes,
their
dysregulated
expression
contributes
significantly
to
various
diseases.
Notably,
they
drive
conditions
like
fibrosis
tumor
metastasis/progression.
To
counter
these
pathologies,
extensive
efforts
have
been
directed
towards
targeting
TGF-βs,
resulting
range
inhibitors.
Despite
some
clinical
success,
agents
yet
reach
full
potential
treatment
cancers.
A
significant
challenge
rests
effectively
TGF-βs’
pathological
functions
while
preserving
roles.
Many
existing
approaches
collectively
target
isoforms,
failing
just
specific
deregulated
ones.
Additionally,
most
strategies
tackle
entire
signaling
pathway
instead
focusing
disease-specific
components
or
preferentially
tumors.
This
review
gives
historical
overview
missed
other
reviews
provides
current
landscape
research,
emphasizing
isoform-specific
disease
implications.
then
delves
into
ongoing
therapeutic
cancer,
stressing
need
more
tools
that
disease-related
components,
advocating
mechanism-based
refined
enhance
effectiveness
TGF-β-targeted
cancer
therapies.
Molecules,
Год журнала:
2021,
Номер
26(17), С. 5420 - 5420
Опубликована: Сен. 6, 2021
Peptide-oligonucleotide
conjugates
(POCs)
represent
one
of
the
increasingly
successful
albeit
costly
approaches
to
increasing
cellular
uptake,
tissue
delivery,
bioavailability,
and,
thus,
overall
efficiency
therapeutic
nucleic
acids,
such
as,
antisense
oligonucleotides
and
small
interfering
RNAs.
This
review
puts
subject
chemical
synthesis
POCs
into
wider
context
problem
acid
drug
cell-penetrating
peptide
structural
types,
mechanisms
their
intracellular
transport,
ways
application,
which
include
formation
non-covalent
complexes
with
(peptide
additives)
or
covalent
conjugation.
The
main
strategies
for
are
viewed
in
detail,
conceptually
divided
(a)
stepwise
solid-phase
approach
(b)
post-synthetic
conjugation
either
solution
on
solid
phase,
especially
by
means
various
click
chemistries.
relative
advantages
disadvantages
both
discussed
compared.
Abstract
Accumulating
research
suggests
that
the
tumor
immune
microenvironment
(TIME)
plays
an
essential
role
in
regulation
of
growth
and
metastasis.
The
cellular
molecular
nature
TIME
influences
cancer
progression
metastasis
by
altering
ratio
immune-
suppressive
versus
cytotoxic
responses
vicinity
tumor.
Targeting
or
activating
components
show
a
promising
therapeutic
avenue
to
combat
cancer.
success
immunotherapy
is
both
astounding
unsatisfactory
clinic.
Advancements
RNA-based
technology
have
improved
understanding
complexity
diversity
its
effects
on
therapy.
TIME-related
RNA
regulators
could
be
targets
for
anticancer
immunotherapy.
In
this
review,
we
discuss
available
immunotherapies
targeting
TIME.
More
importantly,
summarize
potential
various
therapeutics
clinically
treatment.
RNA-dependent
TIME,
as
monotherapy
combined
with
other
evolving
therapeutics,
might
beneficial
patients’
treatment
near
future.
Acta Pharmaceutica Sinica B,
Год журнала:
2022,
Номер
13(4), С. 1429 - 1437
Опубликована: Июль 21, 2022
Evasion
of
apoptosis
is
a
hallmark
cancer,
attributed
in
part
to
overexpression
the
anti-apoptotic
protein
B-cell
lymphoma
2
(Bcl-2).
In
variety
cancer
types,
including
lymphoma,
Bcl-2
overexpressed.
Therapeutic
targeting
has
demonstrated
efficacy
clinic
and
subject
extensive
clinical
testing
combination
with
chemotherapy.
Therefore,
development
co-delivery
systems
for
agents,
such
as
small
interfering
RNA
(siRNA),
chemotherapeutics,
doxorubicin
(DOX),
holds
promise
enabling
therapies.
Lipid
nanoparticles
(LNPs)
are
clinically
advanced
nucleic
acid
delivery
system
compact
structure
suitable
siRNA
encapsulation
delivery.
Inspired
by
ongoing
trials
albumin-hitchhiking
prodrugs,
here
we
developed
DOX-siRNA
strategy
via
conjugation
surface
siRNA-loaded
LNPs.
Our
optimized
LNPs
enabled
potent
knockdown
efficient
DOX
into
nucleus
Burkitts'
(Raji)
cells,
leading
effective
inhibition
tumor
growth
mouse
model
lymphoma.
Based
on
these
results,
our
may
provide
platform
various
acids
new
