Exon-Skipping Therapy for Duchenne Muscular Dystrophy: 30 Years Since Its Proposal and the Future of Pseudoexon Skipping
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1303 - 1303
Опубликована: Фев. 3, 2025
Thirty
years
ago,
in
1995,
I
proposed
a
fundamental
treatment
for
Duchenne
Muscular
Dystrophy
(DMD)
using
antisense
oligonucleotides
(ASOs)
to
induce
exon
skipping
and
restore
dystrophin
expression.
DMD
is
progressive
fatal
muscular
dystrophy,
the
establishment
of
an
effective
therapy
has
been
pressing
demand
among
patients
worldwide.
Exon-skipping
utilizing
ASOs
garnered
significant
attention
as
one
most
promising
treatments
DMD,
stimulating
global
research
development
efforts
ASO
technology.
Two
decades
later,
2016,
was
conditionally
approved
by
U.S.
FDA
first
treatment.
This
review
summarizes
current
status
challenges
ASO-based
exon-skipping
therapies
explores
prospects
pseudoexon
ASOs,
which
holds
potential
achieving
complete
cure
DMD.
Язык: Английский
Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge
Genes,
Год журнала:
2024,
Номер
15(3), С. 359 - 359
Опубликована: Март 13, 2024
Glaesserella
parasuis
(G.
parasuis)
causes
systemic
infection
in
pigs,
but
its
effects
on
skeletal
muscle
and
underlying
mechanisms
are
poorly
understood.
We
investigated
G.
colostrum-deprived
piglets,
observing
decreased
daily
weight
gain
upregulation
of
inflammatory
factors
muscle.
Muscle
fiber
area
diameter
were
significantly
reduced
the
treated
group
(n
=
3)
compared
to
control
3),
accompanied
by
increased
expression
FOXO1,
FBXO32,
TRIM63,
CTSL,
BNIP3.
Based
mRNA
microRNA
(miRNA)
sequencing,
we
identified
1642
differentially
expressed
(DE)
mRNAs
19
known
DE
miRNAs
tissues
between
two
groups.
predicted
target
genes
with
opposite
patterns
found
significant
enrichment
activation
FoxO
signaling
pathway.
that
upregulated
core
effectors
FOXO1
FOXO4
targeted
downregulated
ssc-miR-486,
ssc-miR-370,
ssc-miR-615,
ssc-miR-224.
Further
investigation
showed
their
downstream
involved
protein
degradation
also
ssc-miR-194a-5p,
ssc-miR-194b-5p.
These
findings
suggest
atrophy
piglets
through
accelerated
mediated
“miRNAs-FOXO1/4”
axis,
while
further
research
is
necessary
validate
regulatory
relationships.
Our
results
provide
new
insights
into
understanding
inflammation
growth
caused
role
bacterial
pathogenesis.
Язык: Английский
Spatiotemporal analysis of dystrophin expression during muscle repair
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 8, 2024
Abstract
Dystrophin
mRNA
is
produced
from
a
very
large
genetic
locus
and
transcription
of
single
requires
approximately
16
hours.
This
prolonged
interval
between
transcriptional
initiation
completion
results
in
unusual
behaviour:
skeletal
muscle,
myonuclei
express
dystrophin
continuously
robustly,
yet
degrade
mature
transcripts
shortly
after
completion,
such
that
most
nascent,
not
mature.
implies
expression
principally
controlled
post-transcriptionally,
mechanism
circumvents
delay,
allowing
rapid
responses
to
change
demand.
protein
however
highly
stable,
with
slow
turnover:
healthy
despite
constant
production
mRNA,
demand
low
the
need
for
responsive
minimal.
We
reasoned
this
system
instead
exists
control
during
rare
periods
elevated
but
changing
demand,
as
muscle
development
or
repair,
when
newly
formed
fibres
must
establish
sarcolemmal
rapidly.
By
assessing
regenerating
following
injury,
we
reveal
complex
program
suggests
at
multiple
levels:
nascent
begins
even
prior
myoblast
fusion,
effectively
‘paying
advance’
minimise
subsequent
delay.
During
myotube
differentiation
maturation,
demands
are
high,
increases
only
modestly
while
transcript
stability
markedly
generate
high
numbers
transcripts,
state
persists
until
repair
complete,
oversupply
degradation
resumes.
Our
data
demonstrate
indeed
chiefly
by
turnover,
initiation:
consequently
represents
potential
therapeutic
target
maximising
efficacy
modest
restoration.
Язык: Английский