Clustered
regularly
interspaced
short
palindromic
repeat
(CRISPR)
gene
editing
has
poor
efficacy
and
off-target
side
effect
concerns.
We
herein
report
a
semiconducting
polymer
(SP)-based
nanoCRISPR
system
to
improve
CRISPR
delivery
allow
for
near-infrared
(NIR)
photoactivatable
cancer
therapy.
An
amphiphilic
SP
acts
as
photothermal
converter,
its
backbone
is
grafted
with
single-stranded
deoxyribonucleic
acid
(DNA),
which
enables
hybridization
single
guide
ribonucleic
(sgRNA)
via
complementary
base
pairing
form
sgRNA/SP-DNA.
This
sgRNA/SP-DNA
nanosystem
(nanoCRISPR)
can
effectively
deliver
sgRNA
into
cells
generate
heat
under
NIR
laser
irradiation
the
effect.
The
localized
triggers
dissociation
of
DNA
control
release
sgRNA,
thereby
achieving
precise
regulation
activity.
technology
able
precisely
regulate
expression
green
fluorescent
protein
(GFP)
polo-like
kinase
1
(PLK1)
precision
Chemical Reviews,
Год журнала:
2020,
Номер
120(24), С. 13135 - 13272
Опубликована: Окт. 30, 2020
Photoactivatable
(alternatively,
photoremovable,
photoreleasable,
or
photocleavable)
protecting
groups
(PPGs),
also
known
as
caged
photocaged
compounds,
are
used
to
enable
non-invasive
spatiotemporal
photochemical
control
over
the
release
of
species
interest.
Recent
years
have
seen
development
PPGs
activatable
by
biologically
and
chemically
benign
visible
near-infrared
(NIR)
light.
These
long-wavelength-absorbing
moieties
expand
applicability
this
powerful
method
its
accessibility
non-specialist
users.
This
review
comprehensively
covers
organic
transition
metal-containing
photoactivatable
compounds
(complexes)
that
absorb
in
visible-
NIR-range
various
leaving
gasotransmitters
(carbon
monoxide,
nitric
oxide,
hydrogen
sulfide).
The
text
NIR-light-induced
photosensitized
using
molecular
sensitizers,
quantum
dots,
upconversion
second-harmonic
nanoparticles,
well
via
photodynamic
(photooxygenation
singlet
oxygen)
photothermal
effects.
Release
from
polymers,
micelles,
vesicles,
photoswitches,
along
with
related
emerging
field
photopharmacology,
is
discussed
at
end
review.
Theranostics,
Год журнала:
2020,
Номер
11(2), С. 614 - 648
Опубликована: Окт. 28, 2020
CRISPR/Cas9
genome
editing
has
gained
rapidly
increasing
attentions
in
recent
years,
however,
the
translation
of
this
biotechnology
into
therapy
been
hindered
by
efficient
delivery
materials
target
cells.
Direct
system
as
a
ribonucleoprotein
(RNP)
complex
consisting
Cas9
protein
and
single
guide
RNA
(sgRNA)
emerged
powerful
widespread
method
for
due
to
its
advantages
transient
reduced
off-target
effects.
In
review,
we
summarized
current
RNP
systems
including
physical
approaches
synthetic
carriers.
The
mechanisms
beneficial
roles
these
strategies
intracellular
were
reviewed.
Examples
development
stimuli-responsive
targeted
carriers
are
highlighted.
Finally,
challenges
perspectives
rational
design
next
generation
promising
field
will
be
discussed.
Proceedings of the National Academy of Sciences,
Год журнала:
2022,
Номер
119(26)
Опубликована: Июнь 21, 2022
CRISPR
diagnostics
based
on
nucleic
acid
amplification
faces
barriers
to
its
commercial
use,
such
as
contamination
risks
and
insufficient
sensitivity.
Here,
we
propose
a
robust
solution
involving
optochemical
control
of
RNA
(crRNA)
activation
in
detection.
Based
this
strategy,
recombinase
polymerase
(RPA)
CRISPR-Cas12a
detection
systems
can
be
integrated
into
completely
closed
test
tube.
crRNA
designed
temporarily
inactivated
so
that
RPA
is
not
affected
by
Cas12a
cleavage.
After
the
reaction
completed,
system
activated
under
rapid
light
irradiation.
This
photocontrolled,
fully
diagnostic
avoids
exhibits
more
than
two
orders
magnitude
improvement
sensitivity
compared
with
conventional
one-pot
assay.
photocontrolled
method
was
applied
clinical
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
RNA,
achieving
specificity
comparable
those
PCR.
Furthermore,
compact
automatic
device
constructed.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(23)
Опубликована: Апрель 5, 2023
Abstract
The
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
system
is
a
promising
platform
for
nucleic
acid
detection.
Regulating
the
CRISPR
reaction
would
be
extremely
useful
to
improve
detection
efficiency
and
speed
of
diagnostic
applications.
Here,
we
have
developed
light‐start
CRISPR‐Cas12a
by
employing
caged
RNA
(crRNA).
When
combined
with
recombinase
polymerase
amplification,
robust
photocontrolled
one‐pot
assay
achieved.
simpler
50‐fold
more
sensitive
than
conventional
assay.
This
improved
also
facilitates
development
faster
method.
clinical
samples
demonstrated
that
10–20
min
sufficient
effective
detection,
which
much
current
gold‐standard
technique
PCR.
We
expect
this
advance
in
diagnostics
promote
its
widespread
applications
biomedicine,
agriculture,
food
safety.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(18)
Опубликована: Март 22, 2024
Abstract
DNAzymes
exhibit
tremendous
application
potentials
in
the
field
of
biosensing
and
gene
regulation
due
to
its
unique
catalytic
function.
However,
spatiotemporally
controlled
DNAzyme
activity
remains
a
daunting
challenge,
which
may
cause
nonspecific
signal
leakage
or
silencing
systems.
Here,
we
report
photochemical
approach
via
modular
weaving
active
into
skeleton
tetrahedral
DNA
nanocages
(TDN)
for
light‐triggered
on‐demand
liberation
thus
conditional
control
activity.
We
demonstrate
that
direct
encoding
TDN
could
improve
biostability
ensure
delivery
efficiency,
comparing
with
conventional
surface
anchoring
strategy.
Furthermore,
molecular
nanostructures
allows
remote
DNAzyme‐mediated
high
spatiotemporal
precision
light.
In
addition,
is
applicable
editing
functions
other
functional
nucleic
acids.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(48), С. 22272 - 22280
Опубликована: Ноя. 11, 2022
The
precision
and
therapeutic
potential
of
CRISPR/Cas9
genome
editing
are
greatly
challenged
by
the
less
control
over
Cas9-mediated
DNA
cleavage.
Herein,
we
introduce
a
conditional
cell-selective
system
controlled
disease-associated
enzymes,
termed
enzyme-inducible
CRISPR
(eiCRISPR).
eiCRISPR
comprises
Cas9
protein,
self-blocked
inactive
single-guide
RNA
(bsgRNA),
chemically
caged
deoxyribozyme
(DNAzyme)
that
activates
bsgRNA
in
controllable
manner.
We
design
chemical
modifications
DNAzyme
to
suppress
its
ability
cleave
blocking
region
bsgRNA,
while
decaging
triggered
tumor
cell-overexpressed
enzyme,
for
instance,
NAD(P)H:quinone
oxidoreductase
(NQO1),
restores
activity
switches
on
selectively
cancer
cells.
Moreover,
using
biodegradable
lipid
nanoparticle
deliver
tumor-bearing
xenograft,
show
vivo
activation
enables
human
papillomavirus
18
E6
therapy.
strategy
postsynthetic
site-specific
modification
is
compatible
with
endogenous
chemistries
regulating
targeted
gene
Plant Communications,
Год журнала:
2024,
Номер
5(5), С. 100823 - 100823
Опубликована: Янв. 18, 2024
The
inducible
CRISPR-activation
(CRISPR-a)
system
offers
unparalleled
precision
and
versatility
for
regulating
endogenous
genes,
making
it
highly
sought
after
in
plant
research.
In
this
study,
we
developed
a
chemically
CRISPR-a
tool
called
ER-Tag
by
combining
the
XVE
with
SunTag
system.
We
systematically
compared
different
induction
strategies
achieved
high
efficiency
target
gene
activation.
demonstrated
that
guide
RNAs
could
be
multiplexed
pooled
large-scale
screening
of
effective
morphogenic
genes
pairs
involved
regeneration.
Further
experiments
showed
induced
activation
these
accelerated
regeneration
improved
both
eudicot
monocot
plants,
including
alfalfa,
woodland
strawberry
sheepgrass.
Our
study
expanded
CRISPR
toolset
plants
provided
powerful
new
strategy
studying
functions
when
constitutive
expression
is
not
feasible
or
ideal.
Chemical Society Reviews,
Год журнала:
2021,
Номер
50(18), С. 10403 - 10421
Опубликована: Янв. 1, 2021
Photocaging
groups
provide
spatiotemporal
control
of
function.
This
review
surveys
approaches
to
the
design
and
synthesis
photocaged
peptides
proteins,
provides
an
overview
ways
in
which
these
tools
have
been
applied
answer
biological
questions.