bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 3, 2024
Effective
delivery
of
drug
and
gene
cargos
to
hematopoietic
stem
progenitor
cells
(HSPCs)
is
a
major
challenge.
Current
therapeutic
strategies
in
genetic
disorders
or
hematological
malignancies
are
hindered
by
high
costs,
low
accessibility,
off-target
toxicities.
Layer-by-Layer
nanoparticles
(LbL
NPs)
modular
systems
with
tunable
surface
properties
enable
highly
specific
targeting.
In
this
work,
we
developed
LbL
NPs
that
target
HSPCs
via
antibody
functionalization
reduced
uptake
circulating
myeloid
cells.
layered
poly(acrylic
acid),
bioinert
polymer,
provided
more
stealth
vivo
than
other
tested
bioactive
polyanions.
The
additional
conjugation
anti-cKit
anti-CD90
antibodies
improved
NP
2-
3-fold
non-differentiated
bone
marrow
vitro.
By
contrast,
anti-CD105
functionalized
showed
the
highest
association
vivo,
ranging
from
3.0-8.5%
subpopulations.
This
platform
was
then
adapted
human
HSPC
receptors,
similar
targeting
trends
healthy
CD34+
anti-CXCR4
demonstrated
greatest
B-cell
lymphoma
leukemia
Taken
together,
these
results
underscore
potential
capacity
disease-dependent
context.
Nano Letters,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Systemic
delivery
of
large
nucleic
acids,
such
as
mRNA,
to
the
brain
remains
challenging
in
part
due
blood-brain
barrier
(BBB)
and
tendency
vehicles
accumulate
liver.
Here,
we
design
a
peptide-functionalized
lipid
nanoparticle
(LNP)
platform
for
targeted
mRNA
brain.
We
utilize
click
chemistry
functionalize
LNPs
with
peptides
that
target
receptors
overexpressed
on
endothelial
cells
neurons,
namely
RVG29,
T7,
AP2,
mApoE
peptides.
evaluate
effect
LNP
targeting
neuronal
cell
transfection
vitro,
investigating
factors
serum
protein
adsorption,
intracellular
trafficking,
transcytosis,
exosome
secretion.
Finally,
show
peptide
functionalization
enhances
mouse
reduces
hepatic
after
systemic
administration.
Specifically,
RVG29
improved
vivo,
establishing
its
potential
nonviral
delivering
ACS Nano,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 13, 2025
Effective
delivery
of
drug
and
gene
cargos
to
hematopoietic
stem
progenitor
cells
(HSPCs)
is
a
major
challenge.
Current
therapeutic
strategies
in
genetic
disorders
or
hematological
malignancies
are
hindered
by
high
costs,
low
accessibility,
off-target
toxicities.
Layer-by-layer
nanoparticles
(LbL
NPs)
modular
systems
with
tunable
surface
properties
enable
highly
specific
targeting.
In
this
work,
we
developed
LbL
NPs
that
target
HSPCs
via
antibody
functionalization
reduced
uptake
circulating
myeloid
cells.
layered
poly(acrylic
acid),
bioinert
polymer,
provided
more
stealth
vivo
than
other
tested
bioactive
polyanions.
The
additional
conjugation
anti-cKit
anti-CD90
antibodies
improved
NP
2-
3-fold
nondifferentiated
bone
marrow
vitro.
By
contrast,
anti-CD105
functionalized
showed
the
highest
association
vivo,
ranging
from
3.0
8.5%
subpopulations.
This
platform
was
then
adapted
human
HSPC
receptors,
similar
targeting
trends
healthy
CD34+
anti-CXCR4
demonstrated
greatest
B-cell
lymphoma
leukemia
Taken
together,
these
results
underscore
potential
capacity
disease-dependent
context.
American Journal of Medical Genetics Part C Seminars in Medical Genetics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 24, 2025
ABSTRACT
Advancements
in
molecular
diagnostics
and
the
expanded
understanding
of
pathophysiologic
processes
underlying
a
variety
genetic
conditions
have
led
to
design
implementation
many
targeted
therapies
past
decade.
In
prenatal
space,
these
advancements
rapidly
changed
field
diagnosis
garnered
enthusiasm
toward
interventions
aimed
at
correcting
specific
disease
mechanisms
utero
prevent
irreversible
injury
and/or
leverage
fetal
physiology
increase
effectiveness
treatments.
Although
promising
trials
are
underway,
continued
efforts
fully
elucidate
intricacies
immunology,
blood–brain
barrier
precise
during
different
stages
development
will
be
paramount
refinement
therapies.
The
social
ethical
implications
therapy
also
utmost
importance,
especially
an
era
increasing
restrictions
on
reproductive
autonomy.
This
review
aims
summarize
current
as
well
history
such
endeavors.
Current Opinion in Hematology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 27, 2025
Purpose
of
review
Thalassemia
and
sickle
cell
disease
are
among
the
most
frequent
monogenic
hereditary
diseases.
Access
to
transfusions,
iron
chelation
therapies
drugs
such
as
hydroxyurea
have
improved
life
expectancy
quality
life.
However,
these
diseases
still
cause
significant
disability.
The
first
available
curative
therapy,
bone
marrow
transplantation,
is
unfortunately
not
feasible
for
all
patients.
Over
past
decade,
numerous
studies
focused
on
finding
new
therapies,
many
clinical
trials
evaluated
different
gene
therapy
approaches.
Recent
findings
therapeutic
targets
focus
adding
functional
copies
encoding
β-globin
in
defective
CD34
+
cells,
mainly
using
lentiviral
vectors
directed
towards
HSCs.
More
recently,
has
shifted
inducing
fetal
hemoglobin
production
at
levels
or
repairing
underlying
molecular
defect,
novel
editing
techniques
involving
CRISPR-Cas9,
transcription
activation-like
effector
protein
nucleases,
zinc
finger
nucleases
base
editing.
Preclinical
now
optimizing
how
performed
delivered
reduce
eliminate
myeloablative
treatment
its
potential
adverse
events.
Summary
In
this
review,
we
explore
induce
repair
defect
that
causes
genetically.
Here,
recent
opening
a
era
hemoglobinopathies.
Cancer Drug Resistance,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 28, 2025
Acquired
drug
resistance
is
a
main
factor
contributing
to
cancer
therapy
failure
and
high
mortality,
highlighting
the
necessity
develop
novel
intervention
targets.
Circular
RNAs
(circRNAs),
an
abundant
class
of
RNA
molecules
with
closed
loop
structure,
possess
characteristics
including
stability,
which
provide
unique
advantages
in
clinical
application.
Growing
evidence
indicates
that
aberrantly
expressed
circRNAs
are
associated
against
various
treatments,
targeted
therapy,
chemotherapy,
radiotherapy,
immunotherapy.
Therefore,
targeting
these
aberrant
may
offer
strategy
improve
efficiency
therapy.
Herein,
we
present
summary
most
recently
studied
their
regulatory
roles
on
resistance.
With
advances
artificial
intelligence
(AI)-based
bioinformatics
algorithms,
could
emerge
as
promising
biomarkers
targets
Journal of Craniofacial Surgery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 28, 2025
Fibrous
dysplasia
(FD)
is
a
benign
bone
tumor
consisting
of
fibrotic
deposits
interwoven
with
disorganized
bone.
Craniofacial
FD
characterized
by
progressive
expansile
overgrowth
resulting
in
facial
disfigurement,
vision
loss,
jaw
disfunction,
and
pain.
Diagnosis
often
made
clinical
presentation
suggestive
radiographic
findings,
histologic
genetic
analyses
recommended
questionable
cases.
However,
testing
the
lesions
can
lead
to
false
negatives,
as
contain
both
normal
neoplastic
cells.
To
explore
concordance
between
diagnostic
tools,
we
evaluated
history,
imaging,
histology,
6
Six
subjects
presented
abnormal
bony
imaging
FD.
Histologic
examination
excised
revealed
4
cases
pathologic
findings
consistent
FD,
1
case
diagnosed
juvenile
psammomatoid
ossifying
fibroma
(JPOF),
vascular
malformation.
Given
that
somatic
mosaicism
underpins
pathogenesis,
targeted
sequencing
GNAS
gene
was
performed
from
different
tissue
sources,
including
blood,
lesion,
primary
cell
culture.
pathogenic
variants
were
detected
lesion
all
cases,
demonstrating
JPOF
features.
The
authors
found
mutational
burden
cells
containing
variant
ranges
35.8%
46.8%
31.0%
49.7%
cultured
stromal
variable
correlation
radiographic,
histologic,
molecular
diagnosis
this
study
highlights
heterogeneity
challenges
accurate
diagnosis.
By
culturing
cells,
provide
source
material
for
future
experiments.
