Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(43)
Опубликована: Окт. 20, 2021
Significance
Proteins
are
the
key
drivers
of
neuronal
synaptic
function.
The
regulation
gene
expression
is
important
for
formation
and
modification
synapses
throughout
lifespan.
complexity
dendrites
axons
imposes
unique
challenges
protein
supply
at
remote
locations.
discovery
messenger
RNAs
(mRNAs)
ribosomes
near
has
shown
that
local
synthesis
represents
an
solution
to
this
challenge.
Here
we
used
RNA
sequencing
ribosome
determine
directly
population
mRNAs
present
in
process
translation
cell
bodies,
dendrites,
axons.
Thousands
transcripts
were
differentially
translated
between
body
regions
with
over
800
exhibiting
more
dendritic–axonal
compartment.
Abstract
mRNA
technologies
have
the
potential
to
transform
areas
of
medicine,
including
prophylaxis
infectious
diseases.
The
advantages
for
vaccines
range
from
acceleration
immunogen
discovery
rapid
response
and
multiple
disease
target
manufacturing.
A
greater
understanding
quality
attributes
that
dictate
translation
efficiency,
as
well
a
comprehensive
appreciation
importance
delivery,
are
influencing
new
era
investment
in
development
activities.
application
translational
sciences
growing
early-phase
clinical
experience
continue
inform
candidate
vaccine
selection.
Here
we
review
state
art
prevention
diseases
by
using
pertinent
topics
biotechnology
pharmaceutical
industries.
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.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Ноя. 25, 2019
Abstract
Dynamic
mRNA
modification
in
the
form
of
N
6
-methyladenosine
(m
A)
adds
considerable
richness
and
sophistication
to
gene
regulation.
The
m
A
mark
is
asymmetrically
distributed
along
mature
mRNAs,
with
approximately
35%
residues
located
within
coding
region
(CDS).
It
has
been
suggested
that
methylation
CDS
slows
down
translation
elongation.
However,
neither
decoding
feature
endogenous
mRNAs
nor
physiological
significance
clearly
defined.
Here,
we
found
leads
ribosome
pausing
a
codon-specific
manner.
Unexpectedly,
removing
from
these
transcripts
results
further
decrease
translation.
systemic
analysis
RNA
structural
datasets
revealed
positively
regulates
by
resolving
secondary
structures.
We
demonstrate
elongation-promoting
effect
requires
helicase-containing
reader
YTHDC2.
Our
findings
established
uncovered
non-overlapping
function
proteins.
International Journal of Biological Sciences,
Год журнала:
2021,
Номер
17(6), С. 1446 - 1460
Опубликована: Янв. 1, 2021
The
Coronavirus
disease-19
(COVID-19)
pandemic,
caused
by
severe
acute
respiratory
syndrome
coronavirus
-2
(SARS-CoV-2),
has
impacted
human
lives
in
the
most
profound
ways
with
millions
of
infections
and
deaths.Scientists
pharmaceutical
companies
have
been
race
to
produce
vaccines
against
SARS-CoV-2.Vaccine
generation
usually
demands
years
developing
testing
for
efficacy
safety.However,
it
only
took
less
than
one
year
generate
two
mRNA
from
their
development
deployment.The
rapid
production
time,
cost-effectiveness,
versatility
vaccine
design,
clinically
proven
ability
induce
cellular
humoral
immune
response
crowned
spotlights
as
promising
candidates
fight
pandemic.In
this
review,
we
discuss
general
principles
design
working
mechanisms
vaccines,
provide
an
up-to-date
summary
pre-clinical
clinical
trials
on
seven
anti-COVID-19
candidate
focus
already
licensed
vaccination.In
addition,
highlight
key
strategies
designing
maximize
expression
immunogens
avoid
intrinsic
innate
response.We
also
some
perspective
future
COVID-19
other
pathogens.
Nature Genetics,
Год журнала:
2020,
Номер
52(12), С. 1283 - 1293
Опубликована: Окт. 19, 2020
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
which
causes
COVID-19,
utilizes
angiotensin-converting
enzyme
(ACE2)
for
entry
into
target
cells.
ACE2
has
been
proposed
as
an
interferon-stimulated
gene
(ISG).
Thus,
interferon-induced
variability
in
expression
levels
could
be
important
susceptibility
to
COVID-19
or
its
outcomes.
Here,
we
report
the
discovery
of
a
novel,
transcriptionally
independent
truncated
isoform
ACE2,
designate
deltaACE2
(dACE2).
We
demonstrate
that
dACE2,
but
not
is
ISG.
In
The
Cancer
Genome
Atlas,
dACE2
was
enriched
squamous
tumors
respiratory,
gastrointestinal
and
urogenital
tracts.
vitro,
lacks
356
amino-terminal
amino
acids,
non-functional
binding
SARS-CoV-2
spike
protein
carboxypeptidase.
Our
results
suggest
ISG-type
induction
IFN-high
conditions
created
by
treatments,
inflammatory
tumor
microenvironment
viral
co-infections
unlikely
increase
cellular
promote
infection.
newly
identified
unable
bind
protein.
Truncated
full-length
induced
interferons
viruses,
thus
suggesting
such
are
SARS-CoV-2.