ImmunoHorizons,
Journal Year:
2024,
Volume and Issue:
8(1), P. 97 - 105
Published: Jan. 1, 2024
Abstract
Chimeric
Ag
receptor
(CAR)
NK
cells
are
challenging
to
manufacture
and
fail
achieve
consistent
tumor
infiltration
sustained
cytolytic
function
in
the
microenvironment.
In
vivo
engineering
of
using
mRNA-based
CAR
delivery
may
overcome
these
issues.
this
study,
we
developed
an
programming
method
by
designing
CARs
that
leverage
biology
cell
receptors
for
type–specific
expression
function.
These
were
engineered
fusion
a
recognition
domain
with
natural
cytotoxic
family
including
NKp30,
NKp44,
NKp46.
Our
results
demonstrated
receptor–based
can
engage
endogenous
signaling
adaptors
effectively
activate
human
lysis
cytokine
production.
Specifically,
discovered
stable
NKp44-based
was
contingent
on
presence
immune
cell–specific
adaptor
DAP12.
This
innovative
strategy
facilitates
direct
situ
cells,
enhancing
safety
minimizing
off-target
effects
nontargeted,
healthy
tissues.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
10(19)
Published: April 24, 2023
Ionizable
lipid-based
nanoparticles
(LNPs)
are
the
most
advanced
non-viral
drug
delivery
systems
for
RNA
therapeutics
and
vaccines.
However,
cell
type-specific,
extrahepatic
mRNA
is
still
a
major
hurdle,
hampering
development
of
novel
therapeutic
modalities.
Herein,
ionizable
lipid
library
synthesized
by
modifying
hydrophobic
tail
chains
linkers.
Combined
with
other
helper
lipids
utilizing
microfluidic
mixing
approach,
stable
LNPs
formed.
Using
Luciferase-mRNA,
mCherry
mRNA,
Cre
together
TdTomato
animal
model,
superior
forming
potent
cell-type
specific
identified.
In
vitro
assays
concluded
that
combining
branched
ester
hydroxylamine
linker
negatively
affects
efficiency.
vivo
studies
identify
Lipid
23
as
liver-trophic,
16
type-specific
CD11bhi
macrophage
population
without
an
additional
targeting
moiety.
Finally,
in
efficiency
toxicity
these
compared
SM-102-based
LNP
(Moderna's
formulation)
shown
to
be
cell-specific
LNPs.
Overall,
this
study
suggests
structural
combination
can
drive
functionality
vivo.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 5, 2024
Abstract
Fully
targeted
mRNA
therapeutics
necessitate
simultaneous
organ-specific
accumulation
and
effective
translation.
Despite
some
progress,
delivery
systems
are
still
unable
to
fully
achieve
this.
Here,
we
reformulate
lipid
nanoparticles
(LNPs)
through
adjustments
in
material
structures
compositions
systematically
the
pulmonary
hepatic
(respectively)
distribution
expression.
A
combinatorial
library
of
degradable-core
based
ionizable
cationic
lipids
is
designed,
following
by
optimisation
LNP
compositions.
Contrary
current
paradigms,
our
findings
demonstrate
that
cholesterol
phospholipid
dispensable
for
functionality.
Specifically,
cholesterol-removal
addresses
persistent
challenge
preventing
nanoparticle
tissues.
By
modulating
simplifying
intrinsic
components,
concurrent
translation
achieved
lung
liver,
respectively.
This
targeting
strategy
applicable
existing
with
potential
expand
progress
precise
therapy
diverse
diseases.
Advanced Materials,
Journal Year:
2024,
Volume and Issue:
36(29)
Published: April 24, 2024
Abstract
The
advancement
of
message
RNA
(mRNA)
‐based
immunotherapies
for
cancer
is
highly
dependent
on
the
effective
delivery
(Ribonucleic)
payloads
using
ionizable
lipid
nanoparticles
(LNPs).
However,
clinical
application
these
therapies
hindered
by
variable
mRNA
expression
among
different
types
and
risk
systemic
toxicity.
transient
profile
further
complicates
this
issue,
necessitating
frequent
dosing
thus
increasing
potential
adverse
effects.
Addressing
challenges,
a
high‐throughput
combinatorial
method
utilized
to
synthesize
screen
LNPs
that
efficiently
deliver
circular
(circRNA)
lung
tumors.
lead
LNP,
H1L1A1B3,
demonstrates
fourfold
increase
in
circRNA
transfection
efficiency
cells
over
ALC‐0315,
industry‐standard
LNPs,
while
providing
potent
immune
activation.
A
single
intratumoral
injection
H1L1A1B3
loaded
with
encoding
interleukin‐12
(IL‐12),
induces
robust
response
Lewis
carcinoma
model,
leading
marked
tumor
regression.
Immunological
profiling
treated
tumors
reveals
substantial
increments
CD45
+
leukocytes
enhances
infiltration
CD8
T
cells,
underscoring
ability
modulate
microenvironment
favorably.
These
results
highlight
tailored
LNP
platforms
advance
drug
therapy,
broadening
prospects
immunotherapeutics.
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(11)
Published: March 4, 2024
Carriers
for
RNA
delivery
must
be
dynamic,
first
stabilizing
and
protecting
therapeutic
during
to
the
target
tissue
across
cellular
membrane
barriers
then
releasing
cargo
in
bioactive
form.
The
chemical
space
of
carriers
ranges
from
small
cationic
lipids
applied
lipoplexes
lipid
nanoparticles,
over
medium-sized
sequence-defined
xenopeptides,
macromolecular
polycations
polyplexes
polymer
micelles.
This
perspective
highlights
discovery
distinct
virus-inspired
dynamic
processes
that
capitalize
on
mutual
nanoparticle–host
interactions
achieve
potent
delivery.
From
host
side,
subtle
alterations
pH,
ion
concentration,
redox
potential,
presence
specific
proteins,
receptors,
or
enzymes
are
cues,
which
recognized
by
nanocarrier
via
designs
including
cleavable
bonds,
alterable
physicochemical
properties,
supramolecular
assembly–disassembly
respond
changing
biological
microenvironment
Molecular Cancer,
Journal Year:
2024,
Volume and Issue:
23(1)
Published: June 1, 2024
Abstract
Significant
advancements
have
been
made
in
the
application
of
chimeric
antigen
receptor
(CAR)-T
treatment
for
blood
cancers
during
previous
ten
years.
However,
its
effectiveness
treating
solid
tumors
is
still
lacking,
necessitating
exploration
alternative
immunotherapies
that
can
overcome
significant
challenges
faced
by
current
CAR-T
cells.
CAR-based
immunotherapy
against
shows
promise
with
emergence
macrophages,
which
possess
robust
phagocytic
abilities,
antigen-presenting
functions,
and
ability
to
modify
tumor
microenvironment
stimulate
adaptive
responses.
This
paper
presents
a
thorough
examination
latest
progress
CAR-M
therapy,
covering
both
basic
scientific
studies
clinical
trials.
study
examines
primary
obstacles
hindering
realization
complete
potential
as
well
strategies
be
employed
these
hurdles.
With
revolutionary
technologies
like
situ
genetic
modification,
synthetic
biology
techniques,
biomaterial-supported
gene
transfer,
provide
wider
array
resources
manipulating
tumor-associated
we
suggest
combining
advanced
methods
will
result
creation
new
era
therapy
demonstrates
improved
efficacy,
safety,
availability.
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