ACS Nano,
Год журнала:
2022,
Номер
16(9), С. 14792 - 14806
Опубликована: Авг. 29, 2022
Despite
lipid
nanoparticles'
(LNPs)
success
in
the
effective
and
safe
delivery
of
mRNA
vaccines,
an
inhalation-based
therapy
for
lung
diseases
remains
challenging.
LNPs
tend
to
disintegrate
due
shear
stress
during
aerosolization,
leading
ineffective
delivery.
Therefore,
need
remain
stable
through
process
nebulization
mucus
penetration,
yet
labile
enough
endosomal
escape.
To
meet
these
opposing
needs,
we
utilized
PEG
enhance
surficial
stability
with
inclusion
a
cholesterol
analog,
β-sitosterol,
improve
Increased
concentrations
enhanced
resistance
while
β-sitosterol
provided
polyhedral
shape,
facilitating
The
optimized
exhibited
uniform
particle
distribution,
morphology,
rapid
mucosal
diffusion
gene
transfection.
Inhaled
led
localized
protein
production
mouse
without
pulmonary
or
systemic
toxicity.
Repeated
administration
sustained
lungs.
Lastly,
encoding
cystic
fibrosis
transmembrane
conductance
regulator
(CFTR)
was
delivered
after
CFTR-deficient
animal
model,
resulting
expression
this
therapeutic
protein.
This
study
demonstrated
rational
design
approach
clinical
translation
inhalable
LNP-based
therapies.
Accounts of Chemical Research,
Год журнала:
2021,
Номер
55(1), С. 2 - 12
Опубликована: Дек. 1, 2021
ConspectusLipid
nanoparticles
(LNPs)
are
a
type
of
lipid
vesicles
that
possess
homogeneous
core.
These
widely
used
in
small-molecule
drug
and
nucleic
acid
delivery
recently
gained
much
attention
because
their
remarkable
success
as
platform
for
COVID-19
mRNA
vaccines.
Nonetheless,
the
utility
transient
protein
expression
induced
by
extends
far
beyond
vaccines
against
infectious
diseases─they
also
hold
promise
cancer
vaccines,
replacement
therapies,
gene
editing
components
rare
genetic
diseases.
However,
naked
is
inherently
unstable
prone
to
rapid
degradation
nucleases
self-hydrolysis.
Encapsulation
within
LNPs
protects
from
extracellular
ribonucleases
assists
with
intracellular
delivery.In
this
Account,
we
discuss
core
features
RNA
delivery.
We
focus
our
on
designed
deliver
mRNA;
however,
include
examples
siRNA-LNP
where
appropriate
highlight
commonalities
dissimilarities
due
structure.
First,
introduce
concept
LNPs,
advantages
disadvantages
utilizing
acids
therapeutic
agents,
general
reasoning
behind
molecular
makeup
LNPs.
briefly
most
recent
clinical
successes
LNP-based
therapies.
Second,
describe
theory
methods
LNP
self-assembly.
The
common
idea
all
preparation
inducing
electrostatic
interactions
between
charged
lipids
promoting
nanoparticle
growth
via
hydrophobic
interactions.
Third,
break
down
composition
special
fundamental
properties
purposes
each
component.
This
includes
identified
design
criteria,
commercial
sourcing,
impact
trafficking,
contribution
One
key
ionizable
lipids,
which
initiate
binding
endosomal
membranes
facilitate
cytosolic
release;
roles
other
should
not
be
disregarded,
they
associated
stability,
clearance,
distribution
Fourth,
review
attributes
constructs
whole
can
heavily
influence
size,
charge,
internal
structure,
packing,
membrane
hydration,
affinity
toward
biomacromolecules.
specific
techniques
examine
these
how
adjusted.
Finally,
offer
perspective
future
therapies
some
questions
remain
realm
formulation
optimization.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Май 21, 2022
Abstract
The
therapeutic
use
of
messenger
RNA
(mRNA)
has
fueled
great
hope
to
combat
a
wide
range
incurable
diseases.
Recent
rapid
advances
in
biotechnology
and
molecular
medicine
have
enabled
the
production
almost
any
functional
protein/peptide
human
body
by
introducing
mRNA
as
vaccine
or
agent.
This
represents
rising
precision
field
with
promise
for
preventing
treating
many
intractable
genetic
In
addition,
vitro
transcribed
achieved
programmed
production,
which
is
more
effective,
faster
design
well
flexible
cost-effective
than
conventional
approaches
that
may
offer.
Based
on
these
extraordinary
advantages,
vaccines
characteristics
swiftest
response
large-scale
outbreaks
infectious
diseases,
such
currently
devastating
pandemic
COVID-19.
It
always
been
scientists’
desire
improve
stability,
immunogenicity,
translation
efficiency,
delivery
system
achieve
efficient
safe
mRNA.
Excitingly,
scientific
dreams
gradually
realized
rapid,
amazing
achievements
biology,
technology,
vaccinology,
nanotechnology.
this
review,
we
comprehensively
describe
mRNA-based
therapeutics,
including
their
principles,
manufacture,
application,
effects,
shortcomings.
We
also
highlight
importance
optimization
systems
successful
therapeutics
discuss
key
challenges
opportunities
developing
tools
into
powerful
versatile
genetic,
infectious,
cancer,
other
refractory
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Март 23, 2022
Abstract
To
date,
the
coronavirus
disease
2019
(COVID-19)
caused
by
severe
acute
respiratory
syndrome
2
(SARS-CoV-2)
has
determined
399,600,607
cases
and
5,757,562
deaths
worldwide.
COVID-19
is
a
serious
threat
to
human
health
globally.
The
World
Health
Organization
(WHO)
declared
pandemic
major
public
emergency.
Vaccination
most
effective
economical
intervention
for
controlling
spread
of
epidemics,
consequently
saving
lives
protecting
population.
Various
techniques
have
been
employed
in
development
vaccines.
Among
these,
messenger
RNA
(mRNA)
vaccine
drawing
increasing
attention
owing
its
great
application
prospects
advantages,
which
include
short
cycle,
easy
industrialization,
simple
production
process,
flexibility
respond
new
variants,
capacity
induce
better
immune
response.
This
review
summarizes
current
knowledge
on
structural
characteristics,
antigen
design
strategies,
delivery
systems,
industrialization
potential,
quality
control,
latest
clinical
trials
real-world
data
mRNA
vaccines
as
well
technology.
Current
challenges
future
directions
preventive
infectious
diseases
are
also
discussed.
Chemical Reviews,
Год журнала:
2021,
Номер
121(20), С. 12181 - 12277
Опубликована: Июль 19, 2021
RNA-based
therapeutics
have
shown
great
promise
in
treating
a
broad
spectrum
of
diseases
through
various
mechanisms
including
knockdown
pathological
genes,
expression
therapeutic
proteins,
and
programmed
gene
editing.
Due
to
the
inherent
instability
negative-charges
RNA
molecules,
can
make
most
use
delivery
systems
overcome
biological
barriers
release
payload
into
cytosol.
Among
different
types
systems,
lipid-based
particularly
lipid
nanoparticles
(LNPs),
been
extensively
studied
due
their
unique
properties,
such
as
simple
chemical
synthesis
components,
scalable
manufacturing
processes
LNPs,
wide
packaging
capability.
LNPs
represent
widely
used
for
therapeutics,
evidenced
by
clinical
approvals
three
LNP-RNA
formulations,
patisiran,
BNT162b2,
mRNA-1273.
This
review
covers
recent
advances
lipids,
derivatives,
lipid-derived
macromolecules
over
past
several
decades.
We
focus
mainly
on
structures,
synthetic
routes,
characterization,
formulation
methods,
structure–activity
relationships.
also
briefly
describe
current
status
representative
preclinical
studies
trials
highlight
future
opportunities
challenges.
