Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Aug. 24, 2023
The
proper
transfer
of
genetic
information
from
DNA
to
RNA
protein
is
essential
for
cell-fate
control,
development,
and
health.
Methylation
DNA,
RNAs,
histones,
non-histone
proteins
a
reversible
post-synthesis
modification
that
finetunes
gene
expression
function
in
diverse
physiological
processes.
Aberrant
methylation
caused
by
mutations
or
environmental
stimuli
promotes
various
diseases
accelerates
aging,
necessitating
the
development
therapies
correct
disease-driver
imbalance.
In
this
Review,
we
summarize
operating
system
across
central
dogma,
which
includes
writers,
erasers,
readers,
reader-independent
outputs.
We
then
discuss
how
dysregulation
contributes
neurological
disorders,
cancer,
aging.
Current
small-molecule
compounds
target
modifiers
show
modest
success
certain
cancers.
methylome-wide
action
lack
specificity
lead
undesirable
biological
effects
cytotoxicity,
limiting
their
therapeutic
application,
especially
with
monogenic
cause
different
directions
changes.
Emerging
tools
capable
site-specific
manipulation
hold
great
promise
solve
dilemma.
With
refinement
delivery
vehicles,
these
new
are
well
positioned
advance
basic
research
clinical
translation
field.
Cell,
Journal Year:
2022,
Volume and Issue:
185(14), P. 2559 - 2575.e28
Published: June 9, 2022
A
central
goal
of
genetics
is
to
define
the
relationships
between
genotypes
and
phenotypes.
High-content
phenotypic
screens
such
as
Perturb-seq
(CRISPR-based
with
single-cell
RNA-sequencing
readouts)
enable
massively
parallel
functional
genomic
mapping
but,
date,
have
been
used
at
limited
scales.
Here,
we
perform
genome-scale
targeting
all
expressed
genes
CRISPR
interference
(CRISPRi)
across
>2.5
million
human
cells.
We
use
transcriptional
phenotypes
predict
function
poorly
characterized
genes,
uncovering
new
regulators
ribosome
biogenesis
(including
CCDC86,
ZNF236,
SPATA5L1),
transcription
(C7orf26),
mitochondrial
respiration
(TMEM242).
In
addition
assigning
gene
function,
allow
for
in-depth
dissection
complex
cellular
phenomena—from
RNA
processing
differentiation.
leverage
this
ability
systematically
identify
genetic
drivers
consequences
aneuploidy
discover
an
unanticipated
layer
stress-specific
regulation
genome.
Our
information-rich
genotype-phenotype
map
reveals
a
multidimensional
portrait
function.
Nature Genetics,
Journal Year:
2022,
Volume and Issue:
54(12), P. 1919 - 1932
Published: Dec. 1, 2022
It
remains
unclear
why
acute
depletion
of
CTCF
(CCCTC-binding
factor)
and
cohesin
only
marginally
affects
expression
most
genes
despite
substantially
perturbing
three-dimensional
(3D)
genome
folding
at
the
level
domains
structural
loops.
To
address
this
conundrum,
we
used
high-resolution
Micro-C
nascent
transcript
profiling
in
mouse
embryonic
stem
cells.
We
find
that
enhancer-promoter
(E-P)
interactions
are
largely
insensitive
to
(3-h)
CTCF,
or
WAPL.
YY1
has
been
proposed
as
a
regulator
E-P
loops,
but
also
had
minimal
effects
on
transcription
3D
folding.
Strikingly,
live-cell,
single-molecule
imaging
revealed
reduced
factor
(TF)
binding
chromatin.
Thus,
although
cohesin,
WAPL
is
not
required
for
short-term
maintenance
gene
expression,
our
results
suggest
may
facilitate
TFs
search
bind
their
targets
more
efficiently.
Molecular Cancer,
Journal Year:
2022,
Volume and Issue:
21(1)
Published: March 18, 2022
Abstract
Chimeric
Antigen
Receptor
(CAR)
T-cells
represent
a
breakthrough
in
personalized
cancer
therapy.
In
this
strategy,
synthetic
receptors
comprised
of
antigen
recognition,
signaling,
and
costimulatory
domains
are
used
to
reprogram
target
tumor
cells
for
destruction.
Despite
the
success
approach
refractory
B-cell
malignancies,
optimal
potency
CAR
T-cell
therapy
many
other
cancers,
particularly
solid
tumors,
has
not
been
achieved.
Factors
such
as
exhaustion,
lack
persistence,
cytokine-related
toxicities,
bottlenecks
manufacturing
autologous
products
have
hampered
safety,
effectiveness,
availability
approach.
With
ease
accessibility
CRISPR-Cas9-based
gene
editing,
it
is
possible
address
these
limitations.
Accordingly,
current
research
efforts
focus
on
precision
engineering
with
conventional
CRISPR-Cas9
systems
or
novel
editors
that
can
install
desired
genetic
changes
without
introduction
double-stranded
break
(DSB)
into
genome.
These
tools
strategies
be
directly
applied
targeting
negative
regulators
function,
directing
therapeutic
transgenes
specific
genomic
loci,
generating
reproducibly
safe
potent
allogeneic
universal
on-demand
immunotherapy.
This
review
evaluates
several
ongoing
future
directions
combining
next-generation
editing
biology
optimize
clinical
trials
toward
establishment
new
treatment
paradigm.
Journal of Controlled Release,
Journal Year:
2022,
Volume and Issue:
342, P. 345 - 361
Published: Jan. 10, 2022
The
discovery
of
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
genome
editing
technology
opened
the
door
to
provide
a
versatile
approach
for
treating
multiple
diseases.
Promising
results
have
been
shown
in
numerous
pre-clinical
studies
and
clinical
trials.
However,
safe
effective
method
deliver
genome-editing
components
is
still
key
challenge
vivo
therapy.
Adeno-associated
virus
(AAV)
one
most
commonly
used
vector
systems
date,
but
immunogenicity
against
capsid,
liver
toxicity
at
high
dose,
potential
genotoxicity
caused
by
off-target
mutagenesis
genomic
integration
remain
unsolved.
Recently
developed
transient
delivery
systems,
such
as
virus-like
particle
(VLP)
lipid
nanoparticle
(LNP),
may
solve
some
issues.
This
review
summarizes
existing
possible
solutions
overcome
their
limitations.
Also,
we
highlight
ongoing
trials
therapy
recently
tools
applications.
