Biomedicines,
Год журнала:
2024,
Номер
13(1), С. 47 - 47
Опубликована: Дек. 28, 2024
Gastrointestinal
tumors
present
a
significant
challenge
for
precision
medicine
due
to
their
complexity,
necessitating
the
development
of
more
specific
diagnostic
tools
and
therapeutic
agents.
Recent
advances
have
positioned
coding
non-coding
RNAs
as
emerging
biomarkers
these
malignancies,
detectable
by
liquid
biopsies,
innovative
Many
RNA-based
therapeutics,
such
small
interfering
RNA
(siRNA)
antisense
oligonucleotides
(ASO),
entered
clinical
trials
or
are
available
on
market.
This
review
provides
narrative
examination
potential
in
gastrointestinal
cancers,
with
an
emphasis
its
application
medicine.
discusses
current
challenges,
drug
resistance
tumor
metastasis,
highlights
how
molecules
can
be
leveraged
targeted
detection
treatment.
Additionally,
this
categorizes
targets
based
tissue
type,
offering
comprehensive
analysis
role
advancing
tumors.
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.
Although
small-interfering
RNAs
(siRNAs)
are
specific
silencers
for
numerous
disease-related
genes,
their
clinical
applications
still
require
safe
and
effective
means
of
delivery
into
target
cells.
Highly
efficient
lipid
nanoparticles
(LNPs)
developed
siRNA
delivery,
showcasing
the
advantages
novel
pH-responsive
lipoamino
xenopeptide
(XP)
carriers.
These
sequence-defined
XPs
assembled
by
branched
lysine
linkages
between
cationizable
polar
succinoyl
tetraethylene
pentamine
(Stp)
units
apolar
fatty
acids
(LAFs)
at
various
ratios
bundle
or
U-shape
topologies.
Formulation
siRNA-LNPs
using
LAF
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(11)
Опубликована: Март 4, 2024
Due
to
its
small
size
and
lifelong
optical
transparency,
the
fish
Danionella
cerebrum
is
an
emerging
model
organism
in
biomedical
research.
How
can
this
vertebrate
under
12
mm
length
produce
sounds
over
140
dB?
We
found
that
it
possesses
...Motion
basis
of
nearly
all
animal
behavior.
Evolution
has
led
some
extraordinary
specializations
propulsion
mechanisms
among
invertebrates,
including
mandibles
dracula
ant
claw
pistol
shrimp.
In
contrast,
...
Journal of Controlled Release,
Год журнала:
2024,
Номер
370, С. 239 - 255
Опубликована: Апрель 27, 2024
Double
pH-responsive
xenopeptide
carriers
containing
succinoyl
tetraethylene
pentamine
(Stp)
and
lipo
amino
fatty
acids
(LAFs)
were
evaluated
for
CRISPR/Cas9
based
genome
editing.
Different
carrier
topologies,
variation
of
LAF/Stp
ratios
LAF
types
as
Cas9
mRNA/sgRNA
polyplexes
screened
in
three
different
reporter
cell
lines
using
genomic
targets
(Pcsk9,
eGFP,
mdx
exon
23).
One
U-shaped
bundle
(B2)-shaped
lipo-xenopeptides
exhibiting
remarkable
efficiencies
identified.
Genome
editing
potency
top
observed
at
sub-nanomolar
EC
European Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
205, С. 106983 - 106983
Опубликована: Дек. 7, 2024
Clustered
regularly
interspaced
short
palindromic
repeat
(CRISPR)/CRISPR
associated
(Cas)
protein
has
been
proved
as
a
powerful
tool
for
the
treatment
of
genetic
diseases.
The
Cas9
protein,
when
combined
with
single-guide
RNA
(sgRNA),
forms
Cas9/sgRNA
ribonucleoprotein
(RNP)
capable
targeting
and
editing
genome.
However,
limited
availability
effective
carriers
restricted
broader
application
CRISPR/Cas9
RNP.
In
this
study,
we
evaluated
dual
pH-responsive
amphiphilic
xenopeptides
(XPs)
delivering
These
artificial
lipo-XPs
contain
apolar
cationizable
lipoamino
fatty
acid
(LAF)
polar
oligoaminoethylene
units
such
succinoyl-tetraethylenepentamine
(Stp)
in
various
ratios
U-shaped
topologies.
were
screened
functional
RNP
delivery
four
different
reporter
cell
lines,
including
Duchenne
muscular
dystrophy
(DMD)
exon
skipping
model.
Significantly
enhanced
cellular
uptake
into
HeLa
cells,
endosomal
disruption
gal8-mRuby3
potent
genome
by
several
complexes
was
observed
lines
5
nM
sgRNA
range.
Comparing
mRNA/sgRNA
polyplexes
DMD
model
demonstrated
similar
splice
site
high
two
molecular
modalities.
Based
on
these
studies,
analogues
U1
LAF2-Stp
LAF4-Stp2
structures
deployed,
tuning
amphiphilicity
Stp
group
replacement
six
oligoamino
acids
dmGtp,
chGtp,
dGtp,
Htp,
Stt,
or
GEIPA.
most
(containing
chGtp
GEIPA)
further
gene
efficiency
EC50
values
1
line.
Notably,
LAF2-dGtp
reached
0.51
even
upon
serum
incubation.
Another
carrier
(LAF4-GEIPA2)
complexing
donor
DNA,
facilitated
up
to
43
%
homology-directed
repair
(HDR)
eGFPd2
cells
visualized
switch
from
green
fluorescent
(eGFP)
blue
(BFP).
This
study
presents
system
tunable
RNP/donor
DNA
polyplexes,
offering
an
easily
applicable
strategy
editing.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 19, 2025
Abstract
Endothelial
cells
(EC)
comprise
the
pulmonary
vascular
bed
and
play
a
significant
role
in
health
disease.
Consequently,
EC
niche
represents
an
attractive
therapeutic
target
for
treating
wide
range
of
diseases.
We
have
identified
new
class
dicationic
Charge-Altering
Releasable
Transporters.
These
single-component
transporters
selectively
deliver
mRNA
to
lung
upon
intravenous
administration
without
use
targeting
ligand.
Significantly,
number
spatial
array
cationic
charges
within
repeating
units
CART
polymer
are
found
control
both
delivery
efficacy
tissue
tropism.
High-resolution
imaging
revealed
efficient
endothelial
arteries,
veins
capillaries.
The
selective
tropism
these
CARTs,
coupled
with
tunable
synthesis
this
family
amphiphiles,
enabling
platform
research
clinical
applications.
