Pharmaceutics,
Год журнала:
2023,
Номер
15(2), С. 411 - 411
Опубликована: Янв. 26, 2023
Proteolysis-targeting
chimeras
(PROTACs)
are
rapidly
emerging
as
a
potential
therapeutic
strategy
for
cancer
therapy
by
inducing
the
degradation
of
tumor-overexpressing
oncogenic
proteins.
They
can
specifically
catalyze
target
proteins
recruiting
E3
ligases
and
utilizing
ubiquitin-proteasome
pathway.
Since
their
mode
action
is
universal,
irreversible,
recyclable,
long-lasting,
applicable
to
‘undruggable’
proteins,
PROTACs
gradually
replacing
role
conventional
small
molecular
inhibitors.
Moreover,
application
areas
being
expanded
immunotherapy
various
types
that
involved
in
immunosuppressive
tumor
microenvironments.
However,
poor
water
solubility
low
cell
permeability
considerably
restrict
pharmacokinetic
(PK)
property,
which
necessitates
use
appropriate
delivery
systems
immunotherapy.
In
this
review,
general
characteristics,
developmental
status,
PK
first
briefly
covered.
Next,
recent
studies
on
passive
or
active
targeting
introduced,
effects
tumor-targeting
ability
described.
Finally,
drug
summarized.
The
adoption
an
adequate
system
PROTAC
expected
accelerate
clinical
translation
PROTACs,
well
improve
its
efficacy
therapy.
Abstract
Clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
system
provides
adaptive
immunity
against
plasmids
and
phages
in
prokaryotes.
This
inspires
the
development
of
a
powerful
genome
engineering
tool,
CRISPR/CRISPR-associated
nuclease
9
(CRISPR/Cas9)
editing
system.
Due
to
its
high
efficiency
precision,
CRISPR/Cas9
technique
has
been
employed
explore
functions
cancer-related
genes,
establish
tumor-bearing
animal
models
probe
drug
targets,
vastly
increasing
our
understanding
cancer
genomics.
Here,
we
review
current
status
gene
technology
oncological
research.
We
first
explain
basic
principles
introduce
several
new
CRISPR-based
modes.
next
detail
rapid
progress
CRISPR
screening
revealing
tumorigenesis,
metastasis,
resistance
mechanisms.
In
addition,
delivery
vectors
finally
demonstrate
potential
enhance
effect
adoptive
T
cell
therapy
(ACT)
reduce
adverse
reactions.
Journal of Advanced Research,
Год журнала:
2020,
Номер
29, С. 207 - 221
Опубликована: Окт. 21, 2020
It
is
a
long-standing
goal
of
scientists
and
breeders
to
precisely
control
gene
for
studying
its
function
as
well
improving
crop
yield,
quality,
tolerance
various
environmental
stresses.
The
discovery
modification
CRISPR/Cas
system,
nature-occurred
editing
tool,
opens
an
era
precision
breeding.In
this
review,
we
first
introduce
the
brief
history
followed
mechanism
application
system
on
study
improvement.
Currently,
genome
has
been
becoming
mature
cutting-edge
biotechnological
tool
improvement
that
already
used
in
many
different
traits
crops,
including
pathogen
resistance,
abiotic
tolerance,
plant
development
morphology
even
secondary
metabolism
fiber
development.
Finally,
point
out
major
issues
associating
with
future
research
directions.Key
Scientific
Concepts
Review:
CRISPR/Cas9
robust
powerful
targeting
individual
DNA
RNA
sequence
genome.
can
be
target
knockin,
knockout
replacement
monitoring
regulating
expression
at
epigenome
levels
by
binding
specific
sequence.
Agrobacterium-mediated
method
still
efficient
delivering
regents
into
targeted
cells.
However,
other
delivery
methods,
such
virus-mediated
method,
have
developed
enhanced
potentials
CRISPR/Cas9-based
PAM
requirement
offers
CRISPR/Cas9-targted
genetic
loci
also
limits
CRISPR/Cas9.
Discovering
new
Cas
proteins
modifying
current
enzymes
play
important
role
editing.
Developing
better
methods
eliminating
off-target
effects,
finding
key/master
genes
controlling
growth
two
directions
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(9), С. 7736 - 7736
Опубликована: Апрель 23, 2023
Gene
therapy
is
a
technique
involving
the
modification
of
an
individual’s
genes
for
treating
particular
disease.
The
key
to
effective
gene
efficient
carrier
delivery
system.
Viral
vectors
that
have
been
artificially
modified
lose
their
pathogenicity
are
used
widely
as
system,
with
advantages
natural
high
transduction
efficiency
and
stable
expression.
With
decades
development,
viral
vector-based
therapies
achieved
promising
clinical
outcomes.
Currently,
three
vector
strategies
based
on
adeno-associated
viruses,
adenoviruses,
lentiviruses.
However,
certain
challenges,
such
immunotoxicity
“off-target”,
continue
exist.
In
present
review,
above
discussed
along
respective
therapeutic
applications.
addition,
major
translational
challenges
encountered
in
summarized,
possible
address
these
also
discussed.
Genomics Proteomics & Bioinformatics,
Год журнала:
2022,
Номер
21(1), С. 108 - 126
Опубликована: Март 24, 2022
The
past
decade
has
witnessed
a
rapid
evolution
in
identifying
more
versatile
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)/CRISPR-associated
protein
(Cas)
nucleases
and
their
functional
variants,
as
well
developing
precise
CRISPR/Cas-derived
genome
editors.
programmable
robust
features
of
the
editors
provide
an
effective
RNA-guided
platform
for
fundamental
life
science
research
subsequent
applications
diverse
scenarios,
including
biomedical
innovation
targeted
crop
improvement.
One
most
essential
principles
is
to
guide
alterations
genomic
sequences
or
genes
intended
manner
without
undesired
off-target
impacts,
which
strongly
depends
on
efficiency
specificity
single
RNA
(sgRNA)-directed
recognition
DNA
sequences.
Recent
advances
empirical
scoring
algorithms
machine
learning
models
have
facilitated
sgRNA
design
prediction.
In
this
review,
we
first
briefly
introduce
different
CRISPR/Cas
tools
that
should
be
taken
into
consideration
achieve
specific
purposes.
Secondly,
focus
computer-assisted
resources
are
widely
used
designing
sgRNAs
analyzing
CRISPR/Cas-induced
on-
mutations.
Thirdly,
insights
limitations
available
computational
would
help
researchers
field
further
optimization.
Lastly,
suggest
simple
but
workflow
choosing
applying
web-based
editing.
International Journal for Parasitology Drugs and Drug Resistance,
Год журнала:
2021,
Номер
16, С. 65 - 89
Опубликована: Апрель 27, 2021
Dirofilaria
immitis,
also
known
as
heartworm,
is
a
major
parasitic
threat
for
dogs
and
cats
around
the
world.
Because
of
its
impact
on
health
welfare
companion
animals,
heartworm
disease
huge
veterinary
economic
importance
especially
in
North
America,
Europe,
Asia
Australia.
Within
animal
market
many
different
preventive
products
are
available,
all
which
contain
active
components
same
drug
class,
macrocyclic
lactones.
In
addition
to
compliance
issues,
such
under-dosing
or
irregular
treatment
intervals,
occurrence
drug-resistant
heartworms
within
populations
Mississippi
River
areas
adds
failure
treatments.
The
objective
this
review
provide
an
overview
disease,
summarize
current
control
measures
highlight
potential
new
avenues
best
practices
prevention.
