International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(18), P. 6582 - 6582
Published: Sept. 9, 2020
Messenger
ribonucleic
acid
(mRNA)-based
drugs,
notably
mRNA
vaccines,
have
been
widely
proven
as
a
promising
treatment
strategy
in
immune
therapeutics.
The
extraordinary
advantages
associated
with
including
their
high
efficacy,
relatively
low
severity
of
side
effects,
and
attainment
costs,
enabled
them
to
become
prevalent
pre-clinical
clinical
trials
against
various
infectious
diseases
cancers.
Recent
technological
advancements
alleviated
some
issues
that
hinder
vaccine
development,
such
efficiency
exist
both
gene
translation
vivo
deliveries.
immunogenicity
can
also
be
greatly
adjusted
result
upgraded
technologies.
In
this
review,
we
summarized
details
regarding
the
optimization
underlying
biological
mechanisms
form
vaccines.
Applications
vaccines
cancers
are
introduced.
It
includes
our
prospections
for
applications
caused
by
bacterial
pathogens,
tuberculosis.
At
same
time,
suggestions
future
development
about
storage
methods,
safety
concerns,
personalized
synthesis
found
context.
Vaccines,
Journal Year:
2021,
Volume and Issue:
9(1), P. 65 - 65
Published: Jan. 19, 2021
The
recent
success
of
mRNA
vaccines
in
SARS-CoV-2
clinical
trials
is
part
due
to
the
development
lipid
nanoparticle
delivery
systems
that
not
only
efficiently
express
mRNA-encoded
immunogen
after
intramuscular
injection,
but
also
play
roles
as
adjuvants
and
vaccine
reactogenicity.
We
present
an
overview
then
focus
on
nanoparticles
used
current
trials.
review
concludes
with
analysis
determinants
performance
vaccines.
Pharmaceutics,
Journal Year:
2020,
Volume and Issue:
12(2), P. 102 - 102
Published: Jan. 28, 2020
In
the
past
few
years,
there
has
been
increasing
focus
on
use
of
messenger
RNA
(mRNA)
as
a
new
therapeutic
modality.
Current
clinical
efforts
encompassing
mRNA-based
drugs
are
directed
toward
infectious
disease
vaccines,
cancer
immunotherapies,
protein
replacement
therapies,
and
treatment
genetic
diseases.
However,
challenges
that
impede
successful
translation
these
molecules
into
(i)
mRNA
is
very
large
molecule,
(ii)
it
intrinsically
unstable
prone
to
degradation
by
nucleases,
(iii)
activates
immune
system.
Although
some
have
partially
solved
means
chemical
modification
mRNA,
intracellular
delivery
still
represents
major
hurdle.
The
therapeutics
requires
technologies
can
ensure
stabilization
under
physiological
conditions.
Here,
we
review
opportunities
in
with
non-viral
systems,
present
status
highlight
perspectives
future
this
promising
type
medicine.
Nano Letters,
Journal Year:
2020,
Volume and Issue:
20(3), P. 1578 - 1589
Published: Jan. 17, 2020
Chimeric
antigen
receptor
(CAR)
T
cell
therapy
relies
on
the
ex
vivo
manipulation
of
patient
cells
to
create
potent,
cancer-targeting
therapies,
shown
be
capable
inducing
remission
in
patients
with
acute
lymphoblastic
leukemia
and
large
B
lymphoma.
However,
current
CAR
engineering
methods
use
viral
delivery
vectors,
which
induce
permanent
expression
could
lead
severe
adverse
effects.
Messenger
RNA
(mRNA)
has
been
explored
as
a
promising
strategy
for
transient
mitigate
effects
associated
but
it
most
commonly
requires
electroporation
mRNA
delivery,
can
cytotoxic.
Here,
ionizable
lipid
nanoparticles
(LNPs)
were
designed
human
cells.
A
library
24
lipids
was
synthesized,
formulated
into
LNPs,
screened
luciferase
Jurkat
cells,
revealing
seven
formulations
enhanced
over
lipofectamine.
The
top-performing
LNP
formulation,
C14–4,
selected
primary
This
platform
induced
at
levels
equivalent
electroporation,
substantially
reduced
cytotoxicity.
engineered
via
C14–4
treatment
then
compared
electroporated
coculture
assay
Nalm-6
both
elicited
potent
cancer-killing
activity.
These
results
demonstrate
ability
LNPs
deliver
functional
protein
expression,
indicate
potential
enhance
mRNA-based
methods.
Nucleic Acid Therapeutics,
Journal Year:
2018,
Volume and Issue:
28(3), P. 146 - 157
Published: April 23, 2018
Genetic
drugs
based
on
RNA
or
DNA
have
remarkable
therapeutic
potential
as
virtually
any
disease
can
be
treated
by
silencing
a
pathological
gene,
expressing
beneficial
protein,
editing
defective
genes.
However,
therapies
nucleic
acid
polymers
require
sophisticated
delivery
systems
to
deliver
these
macromolecules
the
interior
of
target
cells.
In
this
study,
we
review
progress
in
developing
nonviral
lipid
nanoparticle
(LNP)
that
attractive
properties,
including
ease
manufacture,
reduced
immune
responses,
multidosing
capabilities,
larger
payloads,
and
flexibility
design.
LNP
represent
most
advanced
for
genetic
it
is
expected
an
LNP-short
interfering
(siRNA)
formulation
will
receive
clinical
approval
from
Food
Drug
Administration
(FDA)
2018
treatment
hereditary
condition
transthyretin-mediated
amyloidosis,
fatal
which
there
currently
no
treatment.
This
achievement
largely
due
development
optimized
ionizable
cationic
lipids,
arguably
important
factor
success
LNP-siRNA.
addition,
highlight
applications,
targeting
tissues
beyond
liver
approaches
messenger
Clustered
Regularly
Interspaced
Short
Palindromic
Repeats/Cas.
Molecular Therapy,
Journal Year:
2019,
Volume and Issue:
27(4), P. 757 - 772
Published: Feb. 10, 2019
In
the
last
two
decades,
there
has
been
growing
interest
in
mRNA-based
technology
for
development
of
prophylactic
vaccines
against
infectious
diseases.
Technological
advancements
RNA
biology,
chemistry,
stability,
and
delivery
systems
have
accelerated
fully
synthetic
mRNA
vaccines.
Potent,
long-lasting,
safe
immune
responses
observed
animal
models,
as
well
encouraging
data
from
early
human
clinical
trials,
make
vaccination
an
attractive
alternative
to
conventional
vaccine
approaches.
Thanks
these
data,
together
with
potential
generic,
low-cost
manufacturing
processes
completely
nature,
prospects
are
very
promising.
addition,
streamline
discovery
development,
facilitate
a
rapid
response
emerging
this
review,
we
overview
unique
attributes
approaches,
review
diseases,
discuss
current
challenges,
highlight
perspectives
about
future
promising
technology.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Feb. 20, 2020
Endosomal
sequestration
of
lipid-based
nanoparticles
(LNPs)
remains
a
formidable
barrier
to
delivery.
Herein,
structure-activity
analysis
cholesterol
analogues
reveals
that
incorporation
C-24
alkyl
phytosterols
into
LNPs
(eLNPs)
enhances
gene
transfection
and
the
length
tail,
flexibility
sterol
ring
polarity
due
-OH
group
is
required
maintain
high
transfection.
Cryo-TEM
displays
polyhedral
shape
for
eLNPs
compared
spherical
LNPs,
while
x-ray
scattering
shows
little
disparity
in
internal
structure.
exhibit
higher
cellular
uptake
retention,
potentially
leading
steady
release
from
endosomes
over
time.
3D
single-particle
tracking
enhanced
intracellular
diffusivity
relative
suggesting
eLNP
traffic
productive
pathways
escape.
Our
findings
show
importance
subcellular
transport
carrying
mRNA
emphasize
need
greater
insights
surface
composition
structural
properties
nanoparticles,
their
interactions
which
enable
designs
improve
endosomal
Vaccines,
Journal Year:
2019,
Volume and Issue:
7(2), P. 37 - 37
Published: April 24, 2019
This
review
provides
a
comparison
of
the
theoretical
issues
and
experimental
findings
for
plasmid
DNA
mRNA
vaccine
technologies.
While
both
have
been
under
development
since
1990s,
in
recent
years,
significant
excitement
has
turned
to
despite
licensure
several
veterinary
vaccines.
Both
required
efforts
increase
their
potency
either
via
manipulating
directly
or
through
addition
adjuvants
immunomodulators
as
well
delivery
systems
formulations.
The
greater
inherent
inflammatory
nature
vaccines
is
discussed
its
potential
immunological
utility
toxicity.
status
clinical
trials
described
along
with
vaccines,
specifically
immunogenicity
licensed
select
candidates
human
trials.
