Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 6, 2024
Abstract
Gene
therapies
provide
treatment
options
for
many
diseases,
but
the
safe
and
long-term
control
of
therapeutic
transgene
expression
remains
a
primary
issue
clinical
applications.
Here,
we
develop
muscone-induced
system
packaged
into
adeno-associated
virus
(AAV)
vectors
(AAV
MUSE
)
based
on
G
protein-coupled
murine
olfactory
receptor
(MOR215-1)
synthetic
cAMP-responsive
promoter
(P
CRE
).
Upon
exposure
to
trigger,
muscone
binds
MOR215-1
activates
cAMP
signaling
pathway
initiate
expression.
AAV
enables
remote,
dose-
exposure-time-dependent
luciferase
in
livers
or
lungs
mice
at
least
20
weeks.
Moreover,
apply
this
treat
two
chronic
inflammatory
diseases:
nonalcoholic
fatty
liver
disease
(NAFLD)
allergic
asthma,
showing
that
inhalation
muscone—after
only
one
injection
—can
achieve
controllable
proteins
(ΔhFGF21
ΔmIL-4).
Our
odorant-molecule-controlled
can
advance
gene-based
precision
human
diseases.
Cell,
Journal Year:
2024,
Volume and Issue:
187(5), P. 1076 - 1100
Published: Feb. 1, 2024
Genome
editing
has
been
a
transformative
force
in
the
life
sciences
and
human
medicine,
offering
unprecedented
opportunities
to
dissect
complex
biological
processes
treat
underlying
causes
of
many
genetic
diseases.
CRISPR-based
technologies,
with
their
remarkable
efficiency
easy
programmability,
stand
at
forefront
this
revolution.
In
Review,
we
discuss
current
state
CRISPR
gene
technologies
both
research
therapy,
highlighting
limitations
that
constrain
them
technological
innovations
have
developed
recent
years
address
them.
Additionally,
examine
summarize
landscape
applications
context
health
therapeutics.
Finally,
outline
potential
future
developments
could
shape
coming
years.
Frontiers in Bioengineering and Biotechnology,
Journal Year:
2024,
Volume and Issue:
11
Published: Jan. 8, 2024
Clustered
regularly
interspaced
short
palindromic
repeat
(CRISPR)-based
genome
editing
(GED)
technologies
have
unlocked
exciting
possibilities
for
understanding
genes
and
improving
medical
treatments.
On
the
other
hand,
Artificial
intelligence
(AI)
helps
achieve
more
precision,
efficiency,
affordability
in
tackling
various
diseases,
like
Sickle
cell
anemia
or
Thalassemia.
AI
models
been
use
designing
guide
RNAs
(gRNAs)
CRISPR-Cas
systems.
Tools
DeepCRISPR,
CRISTA,
DeepHF
capability
to
predict
optimal
a
specified
target
sequence.
These
predictions
take
into
account
multiple
factors,
including
genomic
context,
Cas
protein
type,
desired
mutation
on-target/off-target
scores,
potential
off-target
sites,
impacts
of
on
gene
function
phenotype.
aid
optimizing
different
technologies,
such
as
base,
prime,
epigenome
editing,
which
are
advanced
techniques
introduce
precise
programmable
changes
DNA
sequences
without
relying
homology-directed
repair
pathway
donor
templates.
Furthermore,
AI,
collaboration
with
precision
medicine,
enables
personalized
treatments
based
genetic
profiles.
analyzes
patients'
data
identify
mutations,
variations,
biomarkers
associated
diseases
Cancer,
Diabetes,
Alzheimer's,
etc.
However,
several
challenges
persist,
high
costs,
suitable
delivery
methods
CRISPR
cargoes,
ensuring
safety
clinical
applications.
This
review
explores
AI's
contribution
CRISPR-based
addresses
existing
challenges.
It
also
discusses
areas
future
research
AI-driven
technologies.
The
integration
opens
up
new
genetics,
biomedicine,
healthcare,
significant
implications
human
health.
Genome biology,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: Feb. 1, 2024
Abstract
Protein
function
annotation
has
been
one
of
the
longstanding
issues
in
biological
sciences,
and
various
computational
methods
have
developed.
However,
existing
suffer
from
a
serious
long-tail
problem,
with
large
number
GO
families
containing
few
annotated
proteins.
Herein,
an
innovative
strategy
named
AnnoPRO
was
therefore
constructed
by
enabling
sequence-based
multi-scale
protein
representation,
dual-path
encoding
using
pre-training,
long
short-term
memory-based
decoding.
A
variety
case
studies
based
on
different
benchmarks
were
conducted,
which
confirmed
superior
performance
among
available
methods.
Source
code
models
made
freely
at:
https://github.com/idrblab/AnnoPRO
https://zenodo.org/records/10012272
Trends in Genetics,
Journal Year:
2024,
Volume and Issue:
40(10), P. 891 - 908
Published: Aug. 7, 2024
Harnessing
cutting-edge
technologies
to
enhance
crop
productivity
is
a
pivotal
goal
in
modern
plant
breeding.
Artificial
intelligence
(AI)
renowned
for
its
prowess
big
data
analysis
and
pattern
recognition,
revolutionizing
numerous
scientific
domains
including
We
explore
the
wider
potential
of
AI
tools
various
facets
breeding,
collection,
unlocking
genetic
diversity
within
genebanks,
bridging
genotype–phenotype
gap
facilitate
This
will
enable
development
cultivars
tailored
projected
future
environments.
Moreover,
also
hold
promise
refining
traits
by
improving
precision
gene-editing
systems
predicting
effects
gene
variants
on
phenotypes.
Leveraging
AI-enabled
breeding
can
augment
efficiency
programs
holds
optimizing
cropping
at
grassroots
level.
entails
identifying
optimal
inter-cropping
crop-rotation
models
agricultural
sustainability
field.
Cell,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Biocatalytic
cascades
with
spatial
proximity
can
orchestrate
multistep
pathways
to
form
metabolic
highways,
which
enhance
the
overall
catalytic
efficiency.
However,
effect
of
organization
on
activity
is
poorly
understood,
and
multienzyme
architectural
engineering
predictable
performance
remains
unrealized.
Here,
we
developed
a
standardized
framework,
called
iMARS,
rapidly
design
optimal
architecture
by
integrating
high-throughput
tests
structural
analysis.
The
approach
showed
potential
for
industrial-scale
applications,
artificial
fusion
enzymes
designed
iMARS
significantly
improving
production
resveratrol
45.1-fold
raspberry
ketone
11.3-fold
in
vivo,
as
well
enhancing
ergothioneine
synthesis
fed-batch
fermentation.
In
addition,
greatly
enhanced
vitro
efficiency
complexes
PET
plastic
depolymerization
vanillin
biosynthesis.
As
generalizable
flexible
strategy
at
molecular
level,
could
facilitate
green
chemistry,
synthetic
biology,
biomanufacturing.
ACS Catalysis,
Journal Year:
2025,
Volume and Issue:
15(3), P. 1841 - 1853
Published: Jan. 17, 2025
Acetaldehyde
is
a
toxic
pollutant
that
can
be
detoxified
by
acetaldehyde
dehydrogenases
(ADAs)
through
its
conversion
to
acetyl-CoA.
This
study
developed
an
integrated
approach
combining
virtual
screening,
rational
design,
and
dual
scoring
mechanism
identify
engineer
hyperactive
ADA
variants.
A
library
of
5000
Dickeya
parazeae
(DpADA)
homologues
was
created
protein
BLAST,
deep
learning
tools
predicted
their
Kcat
values.
The
top
100
candidates
were
selected
based
on
binding
affinity,
evaluated
molecular
docking
phylogenetic
analysis.
Among
these,
ADA6
from
Buttiauxella
sp.
S04-F03
exhibited
the
highest
activity,
converting
57.6%
acetyl-CoA,
which
14.1
times
higher
than
DpADA.
To
improve
ADA6's
thermostability,
folding
engineering
applied,
resulting
in
P443C
variant
with
80.7%
increase
residual
activity
after
heat
treatment.
Molecular
dynamics
simulation
pinpointed
I440
as
bottleneck
substrate
tunnel,
guiding
design
dual-scoring
system
integrates
structural
adjustments
electronic
optimization
evaluate
mutations
for
improved
exposure
activity.
final
optimized
variant,
P443C-I440T,
achieved
efficiency
93.2%.
demonstrates
effectiveness
computational
mutagenesis
enhance
enzyme
stability
engineering.
