Journal of Controlled Release,
Journal Year:
2024,
Volume and Issue:
375, P. 776 - 787
Published: Oct. 2, 2024
In
vitro
and
ex-vivo
target
identification
strategies
often
fail
to
predict
in
vivo
efficacy,
particularly
for
glioblastoma
(GBM),
a
highly
heterogenous
tumor
rich
resistant
cancer
stem
cells
(GSCs).
An
screening
tool
can
improve
prediction
of
therapeutic
efficacy
by
considering
the
complex
microenvironment
dynamic
plasticity
GSCs
driving
therapy
resistance
recurrence.
This
study
proposes
lipid
nanoparticles
(LNPs)
as
an
efficient
CRISPR-Cas9
gene
editing
validation
mesenchymal
GSCs.
LNPs
co-delivering
mRNA
(mCas9)
single-guide
RNA
(sgRNA)
were
successfully
formulated
optimized
facilitating
both
editing.
vitro,
achieved
up
67
%
reduction
green
fluorescent
protein
(GFP)
expression,
used
model
target,
outperforming
commercial
transfection
reagent.
Intratumoral
administration
resulted
∼80
GFP
knock-out
2-fold
signal
day
14.
showcases
applicability
potential
GSCs,
currently
lacking
effective
treatment.
By
replacing
with
pool
targets,
proposed
platform
presents
exciting
prospect
orthotopic
bridging
gap
between
preclinical
clinical
research.
Cell,
Journal Year:
2024,
Volume and Issue:
187(5), P. 1076 - 1100
Published: Feb. 1, 2024
Genome
editing
has
been
a
transformative
force
in
the
life
sciences
and
human
medicine,
offering
unprecedented
opportunities
to
dissect
complex
biological
processes
treat
underlying
causes
of
many
genetic
diseases.
CRISPR-based
technologies,
with
their
remarkable
efficiency
easy
programmability,
stand
at
forefront
this
revolution.
In
Review,
we
discuss
current
state
CRISPR
gene
technologies
both
research
therapy,
highlighting
limitations
that
constrain
them
technological
innovations
have
developed
recent
years
address
them.
Additionally,
examine
summarize
landscape
applications
context
health
therapeutics.
Finally,
outline
potential
future
developments
could
shape
coming
years.
The
covalent
attachment
of
polyethylene
glycol
(PEG)
to
therapeutic
agents,
termed
PEGylation,
is
a
well-established
and
clinically
proven
drug
delivery
approach
improve
the
pharmacokinetics
pharmacodynamics
drugs.
Specifically,
PEGylation
can
parent
drug's
solubility,
extend
its
circulation
time,
reduce
immunogenicity,
with
minimal
undesirable
properties.
technology
has
been
applied
various
modalities
including
small
molecules,
aptamers,
peptides,
proteins,
leading
over
30
PEGylated
drugs
currently
used
in
clinic
many
investigational
agents
under
clinical
trials.
Here,
we
summarize
diverse
types
strategies,
key
advantages
therapeutics
their
drugs,
broad
applications
impacts
settings.
A
particular
focus
given
size,
topology,
functionalities
PEG
molecules
utilized
as
well
those
An
additional
section
dedicated
analyzing
some
representative
that
were
discontinued
at
different
stages
studies.
Finally,
critically
discuss
current
challenges
faced
development
translation
agents.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 4, 2023
Abstract
Lipid‐based
nanoparticles
(LBNPs)
are
currently
the
most
promising
vehicles
for
nucleic
acid
drug
(NAD)
delivery.
Although
their
clinical
applications
have
achieved
success,
NAD
delivery
efficiency
and
safety
still
unsatisfactory,
which
are,
to
a
large
extent,
due
existence
of
multi‐level
physiological
barriers
in
vivo.
It
is
important
elucidate
interactions
between
these
LBNPs,
will
guide
more
rational
design
efficient
with
low
adverse
effects
facilitate
broader
therapeutics.
This
review
describes
obstacles
challenges
biological
at
systemic,
organ,
sub‐organ,
cellular,
subcellular
levels.
The
strategies
overcome
comprehensively
reviewed,
mainly
including
physically/chemically
engineering
LBNPs
directly
modifying
by
auxiliary
treatments.
Then
potentials
successful
translation
preclinical
studies
into
clinic
discussed.
In
end,
forward
look
on
manipulating
protein
corona
(PC)
addressed,
may
pull
off
trick
overcoming
those
significantly
improve
efficacy
LBNP‐based
NADs
Chemical Reviews,
Journal Year:
2024,
Volume and Issue:
124(3), P. 929 - 1033
Published: Jan. 29, 2024
RNA-based
therapies
have
catalyzed
a
revolutionary
transformation
in
the
biomedical
landscape,
offering
unprecedented
potential
disease
prevention
and
treatment.
However,
despite
their
remarkable
achievements,
these
encounter
substantial
challenges
including
low
stability,
susceptibility
to
degradation
by
nucleases,
prominent
negative
charge,
thereby
hindering
further
development.
Chemically
modified
platforms
emerged
as
strategic
innovation,
focusing
on
precise
alterations
either
RNA
moieties
or
associated
delivery
vectors.
This
comprehensive
review
delves
into
platforms,
underscoring
significance
augmenting
performance
translational
prospects
of
therapeutics.
It
encompasses
an
in-depth
analysis
various
chemically
that
been
instrumental
propelling
therapeutics
toward
clinical
utility.
Moreover,
scrutinizes
rationale
behind
diverse
chemical
modification
techniques
aiming
at
optimizing
therapeutic
efficacy
molecules,
facilitating
robust
management.
Recent
empirical
studies
corroborating
enhancement
through
modifications
are
highlighted.
Conclusively,
we
offer
profound
insights
transformative
impact
drugs
delineates
prospective
trajectories
for
future
development
integration.
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(11)
Published: March 4, 2024
Nanoparticle-based
RNA
delivery
has
shown
great
progress
in
recent
years
with
the
approval
of
two
mRNA
vaccines
for
Severe
Acute
Respiratory
Syndrome
Coronavirus
2
(SARS-CoV-2)
and
a
liver-targeted
siRNA
therapy.
Here,
we
discuss
preclinical
clinical
advancement
new
generations
therapies
along
multiple
axes.
Improvements
cargo
design
such
as
circularization
data-driven
untranslated
region
optimization
can
drive
better
expression.
New
materials
discovery
research
driven
improved
to
extrahepatic
targets
lung
splenic
immune
cells,
which
could
lead
pulmonary
gene
therapy
cancer
vaccines,
respectively.
Other
organs
even
specific
cell
types
be
targeted
via
conjugation
small
molecule
ligands,
antibodies,
or
peptides
nanoparticles.
Moreover,
response
any
nanoparticle
plays
crucial
role
determining
efficacy.
Targeting
increased
immunogenicity
without
induction
reactogenic
side
effects
is
while
minimization
important
therapies.
developments
have
addressed
each
these
priorities.
Last,
range
trials
targeting
diverse
organs,
types,
diseases
suggest
some
key
advances
that
may
play
next
wave
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(11)
Published: March 4, 2024
Cell-type-specific
in
vivo
delivery
of
genome
editing
molecules
is
the
next
breakthrough
that
will
drive
biological
discovery
and
transform
field
cell
gene
therapy.
Here,
we
discuss
recent
advances
CRISPR-Cas
editors
either
as
preassembled
ribonucleoproteins
or
encoded
mRNA.
Both
strategies
avoid
pitfalls
viral
vector-mediated
offer
advantages
including
transient
editor
lifetime
potentially
streamlined
manufacturing
capability
are
already
proving
valuable
for
clinical
use.
We
review
current
applications
future
opportunities
these
emerging
approaches
could
make
more
efficacious
accessible
future.
