Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology
Emile M. Youssef,
Brandon Fletcher,
Dannelle Palmer
и другие.
Frontiers in Medicine,
Год журнала:
2025,
Номер
11
Опубликована: Янв. 13, 2025
Gene
therapy
has
long
been
a
cornerstone
in
the
treatment
of
rare
diseases
and
genetic
disorders,
offering
targeted
solutions
to
conditions
once
considered
untreatable.
As
field
advances,
its
transformative
potential
is
now
expanding
into
oncology,
where
personalized
therapies
address
immune-related
complexities
cancer.
This
review
highlights
innovative
therapeutic
strategies,
including
gene
replacement,
silencing,
oncolytic
virotherapy,
CAR-T
cell
therapy,
CRISPR-Cas9
editing,
with
focus
on
their
application
both
hematologic
malignancies
solid
tumors.
CRISPR-Cas9,
revolutionary
tool
precision
medicine,
enables
precise
editing
cancer-driving
mutations,
enhancing
immune
responses
disrupting
tumor
growth
mechanisms.
Additionally,
emerging
approaches
target
ferroptosis—a
regulated,
iron-dependent
form
death—offering
new
possibilities
for
selectively
inducing
death
resistant
cancers.
Despite
significant
breakthroughs,
challenges
such
as
heterogeneity,
evasion,
immunosuppressive
microenvironment
(TME)
remain.
To
overcome
these
barriers,
novel
like
dual-targeting,
armored
cells,
combination
checkpoint
inhibitors
ferroptosis
inducers
are
being
explored.
rise
allogeneic
“off-the-shelf”
offers
scalable
more
accessible
options.
The
regulatory
landscape
evolving
accommodate
advancements,
frameworks
RMAT
(Regenerative
Medicine
Advanced
Therapy)
U.S.
ATMP
(Advanced
Therapy
Medicinal
Products)
Europe
fast-tracking
approval
therapies.
However,
ethical
considerations
surrounding
CRISPR-based
editing—such
off-target
effects,
germline
ensuring
equitable
access—remain
at
forefront,
requiring
ongoing
oversight.
Advances
non-viral
delivery
systems,
lipid
nanoparticles
(LNPs)
exosomes,
improving
safety
efficacy
By
integrating
innovations
addressing
concerns,
poised
revolutionize
cancer
treatment,
providing
durable,
effective,
Язык: Английский
Intestinal mucus: the unsung hero in the battle against viral gastroenteritis
Gut Pathogens,
Год журнала:
2025,
Номер
17(1)
Опубликована: Фев. 19, 2025
Intestinal
mucus
plays
a
crucial
role
in
defending
against
enteric
infections
by
protecting
the
vulnerable
intestinal
epithelial
cells
both
physically
and
through
its
various
constituents.
Despite
this,
numerous
gastroenteritis-causing
viruses,
such
as
rotavirus,
coronavirus,
adenovirus,
astrovirus,
calicivirus,
enterovirus,
continue
to
pose
significant
threats
humans
animals.
While
several
studies
have
examined
interactions
between
these
viruses
mucus,
gaps
remain
understanding
full
protective
potential
of
pathogens.
This
review
aims
elucidate
viral
gastroenteritis.
It
begins
with
comprehensive
literature
overview
(i)
(ii)
medical
veterinary
importance,
(iii)
known
mucus.
Following
case
study
is
presented
highlight
age-dependent
blocking
effect
porcine
transmissible
gastroenteritis
virus,
coronavirus.
Finally,
discusses
future
investigation
directions
further
explore
defense
mechanism
stimulate
research
this
dynamic
critical
area.
Язык: Английский
Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics
Chemical Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 17, 2025
The
nascent
field
of
targeted
protein
degradation
(TPD)
could
revolutionize
biomedicine
due
to
the
ability
degrader
molecules
selectively
modulate
disease-relevant
proteins.
A
key
limitation
broad
application
TPD
is
its
dependence
on
small-molecule
ligands
target
proteins
interest.
This
leaves
unstructured
or
those
lacking
defined
cavities
for
binding
out
scope
many
technologies.
use
proteins,
peptides,
and
nucleic
acids
(otherwise
known
as
"biologics")
protein-targeting
moieties
in
degraders
addresses
this
limitation.
In
following
sections,
we
provide
a
comprehensive
critical
review
studies
that
have
used
peptides
mediate
hence
functional
control
otherwise
challenging
targets.
We
describe
existing
platforms
protein/peptide-based
ligand
identification
drug
delivery
systems
might
be
exploited
biologic-based
degraders.
Throughout
Review,
underscore
successes,
challenges,
opportunities
using
protein-based
chemical
biology
tools
spur
discoveries,
elucidate
mechanisms,
act
new
therapeutic
modality.
Язык: Английский
Chromatin structure and gene transcription of recombinant p53 adenovirus vector within host
Frontiers in Molecular Biosciences,
Год журнала:
2025,
Номер
12
Опубликована: Фев. 28, 2025
Introduction
The
recombinant
human
p53
adenovirus
(Ad-p53)
offers
a
promising
approach
for
cancer
therapy,
yet
its
chromatin
structure
and
effects
on
host
organization
gene
expression
are
not
fully
understood.
Methods
In
this
study,
we
employed
in
situ
ChIA-PET
to
investigate
the
colorectal
cell
line
HCT116
with
knockout,
comparing
them
cells
infected
adenovirus-vector
expressing
p53.
We
examined
alterations
interactions
following
treatment
anti-cancer
drug
5-fluorouracil
(5-FU).
Results
Our
results
indicate
that
Ad-p53
forms
specific
architecture
within
vector
mainly
interacts
repressive
or
inactive
regions
of
chromatin,
without
significantly
affecting
associated
genes.
Additionally,
does
affect
topologically
associating
domains
(TADs)
A/B
compartments
genome.
Discussion
These
findings
suggest
while
boosts
expression,
enhancing
sensitivity
substantially
altering
architecture.
Язык: Английский
Engineering an oncolytic adenoviral platform for precise delivery of antisense peptide nucleic acid to modulate PD-L1 overexpression in cancer cells
International Journal of Pharmaceutics,
Год журнала:
2024,
Номер
668, С. 124941 - 124941
Опубликована: Ноя. 10, 2024
Cancer
immunotherapy
is
focused
on
stimulating
the
immune
system
against
cancer
cells
by
exploiting
checkpoint
mechanisms.
PD-1/PD-L1
one
of
most
known
checkpoints
due
to
widespread
upregulation
Programmed
Death
Ligand
1
(PD-L1)
transmembrane
protein
in
tissues.
Accordingly,
taking
advantage
ability
oncolytic
adenoviruses
(OAd)
specifically
infect
and
kill
tumor
over
healthy
ones,
here,
we
developed
a
targeted
delivery
platform
based
OAd
selectively
deliver
an
antisense
peptide
nucleic
acid
(PNA)
targeting
PD-L1
mRNA.
The
PNA
was
modified
with
six-lysine
tail
improve
water
solubility
binding
affinity
polyanionic
surface
carrier.
Dynamic
light
scattering
measurements
confirmed
effective
cargo
OAd.
Flow
cytometry
analysis
evaluated
impact
expression
A549
SK-OV3
cell
lines
post-incubation
OAd/PNA
system.
Statistically
significant
downregulation
observed
treated
OAd-delivered
PNA,
surpassing
effect
free
PNA.
Confocal
microscopy
showed
cytoplasmic
localization
supporting
proposed
mechanism
for
downregulation.
This
holds
potential
enhancing
effectiveness
immunotherapy.
Язык: Английский
Molecular Engineering of Virus Tropism
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11094 - 11094
Опубликована: Окт. 15, 2024
Engineered
viral
vectors
designed
to
deliver
genetic
material
specific
targets
offer
significant
potential
for
disease
treatment,
safer
vaccine
development,
and
the
creation
of
novel
biochemical
research
tools.
Viral
tropism,
specificity
a
virus
infecting
particular
host,
is
often
modified
in
recombinant
viruses
achieve
precise
delivery,
minimize
off-target
effects,
enhance
transduction
efficiency,
improve
safety.
Key
factors
influencing
tropism
include
surface
protein
interactions
between
host-cell,
availability
host-cell
machinery
replication,
host
immune
response.
This
review
explores
current
strategies
modifying
by
altering
their
proteins.
We
provide
an
overview
recent
advancements
targeting
non-enveloped
(adenovirus
adeno-associated
virus)
enveloped
(retro/lentivirus,
Rabies,
Vesicular
Stomatitis
Virus,
Herpesvirus)
cell
types.
Additionally,
we
discuss
approaches,
such
as
rational
design,
directed
evolution,
silico
machine
learning-based
methods,
generating
AAV
variants
with
desired
use
chimeric
envelope
proteins
pseudotyping
viruses.
Finally,
highlight
applications
these
challenges
future
directions
engineering
tropism.
Язык: Английский
Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(24), С. 13300 - 13300
Опубликована: Дек. 11, 2024
The
use
of
3D-printed
gene-activated
bone
grafts
represents
a
highly
promising
approach
in
the
fields
dentistry
and
orthopedics.
Bioresorbable
poly-lactic-co-glycolic
acid
(PLGA)
scaffolds,
infused
with
adenoviral
constructs
that
carry
osteoinductive
factor
genes,
may
provide
an
effective
alternative
to
existing
for
reconstruction
extensive
defects.
This
study
aims
develop
investigate
properties
3D
scaffolds
composed
PLGA
carrying
BMP2
gene
(Ad-BMP2),
both
vitro
vivo.
elastic
modulus
disk-shaped
created
using
specialized
printer
was
determined
by
compressive
testing
axial
radial
directions.
In
cytocompatibility
assessed
adipose-derived
stem
cells
(ADSCs).
ability
Ad-BMP2
transduce
evaluated.
biocompatible
were
also
Young's
exhibited
comparable
values
compression
directions,
measuring
3.4
±
0.7
MPa
3.17
1.4
compression.
promoted
cell
adhesion
had
no
cytotoxic
effect
on
ADSCs.
successfully
transduced
induced
osteogenic
differentiation
vitro.
vivo
studies
demonstrated
properties,
promoting
formation
within
scaffold
filaments
as
well
at
center
critical
calvarial
defect.
Язык: Английский