British Journal of Dermatology,
Journal Year:
2023,
Volume and Issue:
190(5), P. 617 - 627
Published: Dec. 27, 2023
Patients
living
with
inherited
skin
diseases
have
benefited
from
recent
advances
in
DNA
sequencing
technologies
that
provide
new
or
improved
diagnostics.
However,
developing
and
delivering
treatments
for
the
'genodermatoses'
remains
challenging.
The
goal
of
creating
topical
preparations
can
recover
inherent
gene
pathology
largely
aspirational.
progress
two
fields
-
chemistry
delivery
formulations
(lipid
nanoparticles)
molecular
biology
repair
(CRISPR-Cas9,
base
prime
editing)
presents
opportunities
to
address
this
unmet
need.
In
review,
we
discuss
how
lipid
nanoparticle
vehicles
could
be
used
deliver
gene-editing
tools
formulate
'gene
creams'
suitable
treatment
genodermatoses.
We
summarize
historical
landscape
therapeutics
editing
may
herald
an
era
therapies
patients
disorders.
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:
2025,
Volume and Issue:
122(5)
Published: Jan. 30, 2025
The
ionizable
lipid
component
of
nanoparticle
(LNP)
formulations
is
essential
for
mRNA
delivery
by
facilitating
endosomal
escape.
Conventionally,
these
lipids
are
synthesized
through
complex,
multistep
chemical
processes
that
both
time-consuming
and
require
significant
engineering.
Furthermore,
the
development
new
hindered
a
limited
understanding
structure-activity
relationships
effective
delivery.
In
this
work,
we
have
developed
modular
platform
utilizing
Passerini
reaction
to
rapidly
generate
large,
chemically
diverse
libraries
biodegradable
lipids.
This
high-throughput
approach
enables
systematic
exploration
various
components–head
groups,
tails,
spacers–and
their
impacts
on
efficiency.
By
investigating
hydrogen
bonding
potential
between
lipid’s
head
groups
mRNA’s
ribose
phosphate
found
optimizing
methylene
units
linkages
could
enhance
escape
and,
consequently,
efficiencies.
Leveraging
insight,
our
has
led
identification
A4B4-S3,
which
outperforms
current
clinical
benchmark,
SM-102,
in
gene
editing
efficacy
mouse
liver
following
systemic
administration
demonstrates
promise
repeat-dose
protein
replacement
treatments.
work
not
only
offers
rapid,
scalable
method
synthesis
but
also
deepens
relationships,
paving
way
more
therapeutics.
Extracellular Vesicles and Circulating Nucleic Acids,
Journal Year:
2024,
Volume and Issue:
5(3), P. 344 - 57
Published: July 5, 2024
The
rise
of
biologics
and
RNA-based
therapies
challenges
the
limitations
traditional
drug
treatments.
However,
these
potent
new
classes
therapeutics
require
effective
delivery
systems
to
reach
their
full
potential.
Lipid
nanoparticles
(LNPs)
have
emerged
as
a
promising
solution
for
RNA
delivery,
but
endosomal
entrapment
remains
critical
barrier.
In
contrast,
natural
extracellular
vesicles
(EVs)
possess
innate
mechanisms
overcome
degradation,
demonstrating
superior
escape
(EE)
compared
conventional
LNPs.
This
mini
review
explores
EE
lipid
nanoparticle-based
offers
insights
into
EV
advance
LNP
design
therapeutics.
We
compare
strategies
EVs
with
those
used
in
LNPs
highlight
contemporary
approaches.
By
understanding
EE,
we
will
be
able
develop
more
vehicles,
enhancing
efficacy
therapies.
Advanced Functional Materials,
Journal Year:
2024,
Volume and Issue:
34(21)
Published: Feb. 1, 2024
Abstract
Messenger
RNA
(mRNA)
has
emerged
as
a
promising
therapeutic
modality
for
various
diseases.
However,
efficient
delivery
of
mRNA
into
target
cells
remains
significant
challenge.
In
this
study,
the
combinatorial
synthesis
and
characterization
novel
series
ionizable
biscarbamate
lipids
(IBLs)
lipid
nanoparticle
(LNP)
are
reported.
A
simplified
scalable
method
is
developed,
resulting
in
IBLs
suitable
formulating
stable
LNPs.
Two
generations
synthesized
evaluated
their
transfection
capacity
vitro,
using
eGFP
reporter
protein,
leading
to
identification
S‐Ac7‐DOG
lead
IBL.
Upon
intramuscular
vaccination,
LNPs
instigated
robust
antigen‐specific
CD8+
T
cell
responses
against
an
encoded
viral
oncoprotein
tumor
neo‐antigen.
comparison
MC3
LNPs,
which
used
benchmark,
exhibit
low
reactogenicity,
transfection,
distinct
biodistribution,
with
higher
accumulation
draining
lymph
nodes
spleen.
These
findings
highlight
potential
class
vaccines
beyond.
Expert Opinion on Drug Delivery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 11, 2025
Introduction
mRNA
therapeutics
were
a
niche
area
in
drug
development
before
COVIDvaccines.
Now
they
are
used
vaccine
development,
for
non-viral
therapeuticgenome
editing,
vivo
chimericantigen
receptor
T
(CAR
T)
celltherapies
and
protein
replacement.
mRNAis
large,
charged,
easily
degraded
by
nucleases.
It
cannot
get
into
cells,escape
the
endosome,
be
translated
to
disease-modifying
without
adelivery
system
such
as
lipid
nanoparticles
(LNPs).
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 17, 2025
Abstract
Lipid
nanoparticles
(LNPs)
are
clinically
advanced
delivery
systems
for
RNA.
The
extensively
developed
structure
of
ionizable
lipids
greatly
contributes
to
the
functional
mRNA.
However,
endosomal
escape
is
one
severe
biological
barriers
that
continue
render
this
process
inefficient
(e.g.,
less
than
10%).
Although
LNPs
contain
phospholipids,
their
role
poorly
understood,
and
there
have
been
few
attempts
perform
chemical
engineering
required
improve
functionality.
Herein,
a
cubic
phase‐inducible
fusogenic
zwitterionic
phospholipid
derived
from
1,2‐dioleoyl‐3‐
sn
‐glycero‐phosphoethanolamine
(DOPE),
DOPE‐Cx
described,
designed
correct
problem.
orientation
head
group
DOPE
engineered
by
attaching
series
hydrophobic
moieties
intermolecular
interaction
with
phosphatidylcholine
(PC),
followed
lipid‐phase
transition
into
non‐lamellar
phases
facilitate
membrane
fusion‐mediated
escape.
A
structure–activity
relationship
study
reveals
small
chains
induce
instead
hexagonal
phase
when
mixed
PC,
which
enhances
mRNA
in
liver
as
opposed
action
typically
utilized
naturally
occurring
phospholipids.
Engineered
functionalized
phospholipids
will
be
great
value
therapeutic
applications
mRNAs.
Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology,
Journal Year:
2024,
Volume and Issue:
16(4)
Published: July 1, 2024
Abstract
mRNA
therapeutics
have
shown
great
potential
for
a
broad
spectrum
of
disease
treatment.
However,
the
challenges
mRNA's
inherent
instability
and
difficulty
in
cellular
entry
hindered
its
progress
biomedical
field.
To
address
barriers
deliver
to
cells
interest,
various
delivery
systems
are
designed.
Among
these,
lipid
nanoparticles
(LNPs)
stand
out
as
most
extensively
used
systems,
particularly
following
clinical
approvals
corona
virus
2019
(COVID‐19)
vaccines.
LNPs
comprised
ionizable
cationic
lipids,
phospholipids,
cholesterol,
polyethylene
glycol
derived
lipids
(PEG‐lipids).
In
this
review,
we
primarily
summarize
recent
advancements
LNP
technology,
focusing
on
structures
four
constituents
their
applications.
We
delve
into
structure–activity
relationships
while
also
exploring
future
prospects
developing
more
efficacious
systems.
This
article
is
categorized
under:
Therapeutic
Approaches
Drug
Discovery
>
Emerging
Technologies
Biology‐Inspired
Nanomaterials
Lipid‐Based
Structures
Nanotechnology
Biology
Nanoscale
Systems
