bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 20, 2023
ABSTRACT
Messenger
RNA
(mRNA)
has
emerged
as
an
attractive
therapeutic
molecule
for
a
plethora
of
clinical
applications.
For
in
vivo
functionality,
mRNA
therapeutics
require
encapsulation
into
effective,
stable,
and
safe
delivery
systems
to
protect
the
cargo
from
degradation
reduce
immunogenicity.
Here,
bioengineering
platform
efficient
loading
functional
using
bionormal
nanoparticles,
Extracellular
Vesicles
(EVs),
is
established
by
expressing
highly
specific
RNA-binding
domain
fused
CD63
EV
producer
cells
stably
target
mRNA.
The
additional
combination
with
fusogenic
endosomal
escape
moiety,
VSVg,
enables
at
doses
substantially
lower
than
currently
used
clinically
synthetic
lipid-based
nanoparticles.
Importantly,
application
EVs
loaded
effective
cancer
immunotherapy
proves
aggressive
melanoma
mouse
model.
This
technology
addresses
substantial
drawbacks
associated
EV-based
nucleic
acid
leap
forward
Graphical
Abstract
(Figure
created
BioRender)
Advanced Materials,
Год журнала:
2024,
Номер
36(33)
Опубликована: Июнь 27, 2024
Extracellular
vesicles
(EVs)
are
promising
next-generation
therapeutics
and
drug
delivery
systems
due
to
demonstrated
safety
efficacy
in
preclinical
models
early-stage
clinical
trials.
There
is
an
urgent
need
address
the
immunogenicity
of
EVs
(beyond
apparent
lack
immunotoxicity)
advance
development.
To
date,
few
studies
have
assessed
unintended
immunological
recognition
EVs.
An
in-depth
understanding
EV-induced
clearance
necessary
develop
effective
therapeutic
strategies,
including
approaches
mitigate
when
undesired.
This
article
summarizes
various
factors
involved
potential
strategies
reduce
for
improved
benefit.
Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials,
Год журнала:
2024,
Номер
151, С. 106391 - 106391
Journal of Extracellular Vesicles,
Год журнала:
2024,
Номер
13(6)
Опубликована: Июнь 1, 2024
Abstract
Mesenchymal
stromal
cells
(MSCs)
are
promising
regenerative
therapeutics
that
primarily
exert
their
effects
through
secreted
extracellular
vesicles
(EVs).
These
EVs
–
being
small
and
non‐living
easier
to
handle
possess
advantages
over
cellular
products.
Consequently,
the
therapeutic
potential
of
MSC‐EVs
is
increasingly
investigated.
However,
due
variations
in
MSC‐EV
manufacturing
strategies,
products
should
be
considered
as
highly
diverse.
Moreover,
diverse
array
EV
characterisation
technologies
used
for
further
complicates
reliable
interlaboratory
comparisons
published
data.
this
study
aimed
establish
a
common
method
can
easily
by
various
researchers
characterise
preparations
facilitate
comparisons.
To
end,
we
conducted
comprehensive
inter‐laboratory
assessment
using
novel
multiplex
bead‐based
flow
cytometry
assay
panel.
This
involved
11
different
from
five
laboratories
with
varying
MSC
sources,
culture
conditions,
preparation
methods.
Through
panel
covering
range
mostly
MSC‐related
markers,
identified
set
cell
surface
markers
consistently
positive
(CD44,
CD73
CD105)
or
negative
(CD11b,
CD45
CD197)
on
all
explored
preparations.
Hierarchical
clustering
analysis
revealed
distinct
marker
profiles
associated
specific
processes
laboratory
conditions.
We
propose
CD73,
CD105
CD44
robust
minimally
identifying
MSC‐derived
CD11b,
CD14,
CD19,
CD79
markers.
Additionally,
highlight
influence
medium
components,
particularly
human
platelet
lysate,
profiles,
underscoring
conditions
resulting
standardisable
approach
profiling
offers
tool
routine
manufactured
pre‐clinical
clinical
research,
enhances
quality
control
preparations,
hopefully
paves
way
higher
consistency
reproducibility
emerging
field.
Protein & Cell,
Год журнала:
2024,
Номер
15(10), С. 724 - 743
Опубликована: Март 22, 2024
Abstract
Developing
an
intracellular
delivery
system
is
of
key
importance
in
the
expansion
protein-based
therapeutics
acting
on
cytosolic
or
nuclear
targets.
Recently,
extracellular
vesicles
(EVs)
have
been
exploited
as
next-generation
modalities
due
to
their
natural
role
intercellular
communication
and
biocompatibility.
However,
fusion
protein
interest
a
scaffold
represents
widely
used
strategy
for
cargo
enrichment
EVs,
which
could
compromise
stability
functionality
cargo.
Herein,
we
report
via
EV-based
approach
(IDEA)
that
efficiently
packages
delivers
native
proteins
both
vitro
vivo
without
use
scaffold.
As
proof-of-concept,
applied
IDEA
deliver
cyclic
GMP-AMP
synthase
(cGAS),
innate
immune
sensor.
The
results
showed
cGAS-carrying
EVs
activated
interferon
signaling
elicited
enhanced
antitumor
immunity
multiple
syngeneic
tumor
models.
Combining
cGAS
with
checkpoint
inhibition
further
synergistically
boosted
efficacy
vivo.
Mechanistically,
scRNA-seq
demonstrated
mediated
significant
remodeling
intratumoral
microenvironment,
revealing
pivotal
infiltrating
neutrophils
milieu.
Collectively,
IDEA,
universal
facile
strategy,
can
be
expand
advance
development
therapeutics.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 9, 2024
Abstract
Messenger
RNA
(mRNA)
has
emerged
as
an
attractive
therapeutic
molecule
for
a
plethora
of
clinical
applications.
For
in
vivo
functionality,
mRNA
therapeutics
require
encapsulation
into
effective,
stable,
and
safe
delivery
systems
to
protect
the
cargo
from
degradation
reduce
immunogenicity.
Here,
bioengineering
platform
efficient
loading
functional
using
bionormal
nanoparticles,
extracellular
vesicles
(EVs),
is
established
by
expressing
highly
specific
RNA‐binding
domain
fused
CD63
EV
producer
cells
stably
target
mRNA.
The
additional
combination
with
fusogenic
endosomal
escape
moiety,
Vesicular
Stomatitis
Virus
Glycoprotein,
enables
at
doses
substantially
lower
than
currently
used
clinically
synthetic
lipid‐based
nanoparticles.
Importantly,
application
EVs
loaded
effective
cancer
immunotherapy
proves
aggressive
melanoma
mouse
model.
This
technology
addresses
substantial
drawbacks
associated
EV‐based
nucleic
acid
leap
forward
Extracellular
vesicles
(EVs)
are
cell
derived
nanovesicles
which
implicated
in
both
physiological
and
pathological
intercellular
communication,
including
the
initiation,
progression,
metastasis
of
cancer.
The
exchange
biomolecules
between
stromal
cells
cancer
via
EVs
can
provide
a
window
to
monitor
development
real
time
for
better
diagnostic
interventional
strategies.
In
addition,
process
secretion
internalization
by
tumor
microenvironment
(TME)
be
exploited
delivering
therapeutics.
have
potential
targeted,
biocompatible,
efficient
delivery
platform
treatment
other
diseases.
Natural
as
well
engineered
nanomedicine
immense
disease
intervention.
Here,
we
an
overview
current
knowledge
EVs'
function
therapeutic
applications
setting,
EV
engineering
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Май 21, 2024
Inflammation
plays
a
critical
role
in
conditions
such
as
acute
liver
failure,
acute-on-chronic
and
ischemia-reperfusion-induced
injury.
Various
pathogenic
pathways
contribute
to
inflammation,
involving
inflammatory
polarization
of
macrophages
Küpffer
cells,
neutrophil
infiltration,
dysregulation
T
cell
subsets,
oxidative
stress,
activation
hepatic
stellate
cells.
While
mesenchymal
stromal
cells
(MSCs)
have
demonstrated
beneficial
properties,
their
clinical
translation
is
limited
by
cellular
nature.
However,
MSC-derived
extracellular
vesicles
(MSC-EVs)
emerged
promising
cell-free
therapeutic
approach
for
immunomodulation.
MSC-EVs
naturally
mirror
parental
overcoming
the
limitations
associated
with
use
MSCs.
In
vitro
vivo
preclinical
studies
that
replicate
effects
MSCs
This
includes
reduction
death
improvement
hepatocyte
function,
induction
immunomodulatory
effects,
mitigation
cytokine
storm.
Nevertheless,
face
challenges
regarding
necessity
defining
consistent
isolation
methods,
optimizing
culture
conditions,
establishing
quality
control
measures
EV
characterization
functional
assessment.
By
standardized
protocols,
guidelines,
affordable
cost
mass
production,
clinicians
researchers
will
solid
foundation
conduct
further
studies,
validate
efficacy
MSC-EVs,
ultimately
pave
way
implementation
