bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 31, 2024
Abstract
mRNA
delivery
offers
new
opportunities
for
disease
treatment
by
directing
cells
to
produce
therapeutic
proteins.
However,
designing
highly
stable
mRNAs
with
programmable
cell
type-specificity
remains
a
challenge.
To
address
this,
we
measured
the
regulatory
activity
of
60,000
5’
and
3’
untranslated
regions
(UTRs)
across
six
types
developed
PARADE
(Prediction
And
RAtional
DEsign
UTRs),
generative
AI
framework
engineer
RNA
tailored
type-specific
activity.
We
validated
testing
15,800
de
novo-designed
sequences
these
lines
identified
many
that
demonstrated
superior
specificity
compared
existing
therapeutics.
PARADE-engineered
UTRs
also
exhibited
robust
tissue-specific
in
animal
models,
achieving
selective
expression
liver
spleen.
leveraged
enhance
stability,
significantly
increasing
protein
output
durability
vivo.
These
advancements
translated
notable
increases
efficacy,
as
PARADE-designed
oncosuppressor
mRNAs,
namely
PTEN
P16,
effectively
reduced
tumor
growth
patient-derived
neuroglioma
xenograft
models
orthotopic
mouse
models.
Collectively,
findings
establish
versatile
platform
safer,
more
precise,
therapies.
The Plant Journal,
Год журнала:
2025,
Номер
121(5)
Опубликована: Март 1, 2025
Plants
are
essential
for
human
survival.
Over
the
past
three
decades,
work
with
reference
plant
Arabidopsis
thaliana
has
significantly
advanced
biology
research.
One
key
event
was
sequencing
of
its
genome
25
years
ago,
which
fostered
many
subsequent
research
technologies
and
datasets.
been
instrumental
in
elucidating
plant-specific
aspects
biology,
developing
tools,
translating
findings
to
crop
improvement.
It
not
only
serves
as
a
model
understanding
but
also
other
fields,
discoveries
having
led
applications
health,
including
insights
into
immunity,
protein
degradation,
circadian
rhythms.
development
tools
useful
wider
biological
community,
such
optogenetic
systems
auxin-based
degrons.
This
4th
Multinational
Steering
Committee
Roadmap
outlines
future
directions,
emphasis
on
computational
approaches,
support,
translation
crops,
conference
accessibility,
coordinated
efforts,
climate
change
mitigation,
sustainable
production,
fundamental
will
remain
nexus
discovery,
innovation,
application,
driving
advances
both
year
2030,
beyond.
Artificial
intelligence
(AI)
is
becoming
a
transformative
force
in
the
life
sciences,
pushing
boundaries
of
possibility.
Imagine
AI
automating
time-consuming
tasks,
uncovering
hidden
patterns
vast
datasets,
designing
proteins
minutes
instead
years,
and
even
predicting
disease
outbreaks
before
they
occur.
This
review
explores
latest
tools
revolutionizing
scientific
fields,
including
research
data
analysis,
healthcare,
supporting
writing.
Beyond
processing,
reshaping
how
scientists
draft
share
their
findings,
enhancing
processes
ranging
from
literature
reviews
to
citation
management.
However,
with
great
power
comes
responsibility.
Are
we
prepared
for
this
leap?
delves
into
forefront
where
innovation
meets
Genome Research,
Год журнала:
2024,
Номер
34(9), С. 1411 - 1420
Опубликована: Сен. 1, 2024
Cis
-regulatory
elements
(CREs),
such
as
promoters
and
enhancers,
are
DNA
sequences
that
regulate
the
expression
of
genes.
The
activity
a
CRE
is
influenced
by
order,
composition,
spacing
sequence
motifs
bound
proteins
called
transcription
factors
(TFs).
Synthetic
CREs
with
specific
properties
needed
for
biomanufacturing
well
many
therapeutic
applications
including
cell
gene
therapy.
Here,
we
present
regLM,
framework
to
design
synthetic
desired
properties,
high,
low,
or
type–specific
activity,
using
autoregressive
language
models
in
conjunction
supervised
sequence-to-function
models.
We
used
our
yeast
human
enhancers.
demonstrate
generated
approach
not
only
predicted
have
functionality
but
also
contain
biological
features
similar
experimentally
validated
CREs.
regLM
thus
facilitates
realistic
regulatory
while
providing
insights
into
cis
code.
Medicine,
Год журнала:
2025,
Номер
104(3), С. e41300 - e41300
Опубликована: Янв. 17, 2025
Rationale:
Microcephaly,
epilepsy,
and
developmental
delay
(MCSZ)
is
a
rare
neurodevelopmental
disorder
associated
with
autosomal
recessive
inheritance
of
mutations
in
the
polynucleotide
kinase
3’-phosphatase
(PNKP)
gene.
Prompt
identification
management
are
essential,
as
delayed
diagnosis
or
intervention
may
result
severe
complications
mortality.
In
this
case,
prenatal
screening
second
trimester
detected
fetal
microcephaly
gradual
decline
head
circumference,
prompting
decision
to
terminate
pregnancy.
Subsequent
genetic
analysis
tissue
confirmed
presence
compound
heterozygous
PNKP
Patient
concerns:
The
patient,
34-year-old
remarried
female
no
history
consanguineous
marriage,
underwent
2
mid-trimester
termination
procedures
due
sought
counseling
for
reproductive
assistance.
Diagnoses:
patient’s
carrier
status
was
ascertained
through
whole-exome
sequencing
molecular
testing
monogenic
disorders.
terminated
fetus
diagnosed
MCSZ,
condition
Interventions:
Fetal
identified
via
ultrasound,
leading
pregnancy
during
same
trimester.
immediate
family
revealed
gene
underlying
cause
MCSZ.
Genetic
provided,
followed
by
1
cycle
preimplantation
monogenic.
Outcomes:
patient
carried
c.1188
+
1G
>
A
mutation,
whereas
her
husband
c.976G
mutation.
found
have
A.
After
counseling,
couple
monogenic,
unfortunately,
occurred
after
embryos
were
transferred.
Lessons:
caused
mutations,
exceedingly
rare.
Women
adverse
outcomes
should
undergo
close
monitoring
checkups.
If
detected,
it
essential
strictly
follow
obstetric
guidelines
care,
such
comprehensive
cranial
magnetic
resonance
imaging
confirmation.
Avoidance
marriages
advised.
Early
detection
timely
key
preventing
outcomes.
