Theranostics,
Год журнала:
2023,
Номер
13(13), С. 4526 - 4558
Опубликована: Янв. 1, 2023
Drug
evaluation
has
always
been
an
important
area
of
research
in
the
pharmaceutical
industry.
However,
animal
welfare
protection
and
other
shortcomings
traditional
drug
development
models
pose
obstacles
challenges
to
evaluation.
Organ-on-a-chip
(OoC)
technology,
which
simulates
human
organs
on
a
chip
physiological
environment
functionality,
with
high
fidelity
reproduction
organ-level
physiology
or
pathophysiology,
exhibits
great
promise
for
innovating
pipeline.
Meanwhile,
advancement
artificial
intelligence
(AI)
provides
more
improvements
design
data
processing
OoCs.
Here,
we
review
current
progress
that
made
generate
OoC
platforms,
how
single
multi-OoCs
have
used
applications,
including
testing,
disease
modeling,
personalized
medicine.
Moreover,
discuss
issues
facing
field,
such
as
large
reproducibility,
point
integration
OoCs
AI
analysis
automation,
is
benefit
future
Finally,
look
forward
opportunities
faced
by
coupling
AI.
In
summary,
advancements
development,
combinations
AI,
will
eventually
break
state
The Journal of Gene Medicine,
Год журнала:
2024,
Номер
26(8)
Опубликована: Авг. 1, 2024
Abstract
To
date,
3,900
gene
therapy
clinical
trials
have
been
completed,
are
ongoing
or
approved
worldwide.
Our
database
brings
together
global
information
on
activity
from
trial
databases,
official
agency
sources,
published
literature,
conference
presentations
and
posters
kindly
provided
to
us
by
individual
investigators
sponsors.
This
review
presents
our
analysis
of
that,
the
best
knowledge,
being
performed
As
March
2023
update,
we
entries
undertaken
in
46
countries.
We
analyzed
geographical
distribution
trials,
disease
indications
(or
other
reasons)
for
proportions
which
different
vector
types
used,
genes
transferred.
Details
analyses
presented,
searchable
The
Journal
Gene
Medicine
Therapy
Clinical
Trials
Worldwide
website
at
https://a873679.fmphost.com/fmi/webd/GTCT
.
also
provide
an
overview
progress
made
around
world,
discuss
key
trends
since
previous
review,
namely
unprecedented
increase
activity,
including
implementation
genome
editing
technology
with
potential
transform
field
moving
forward.
Lab on a Chip,
Год журнала:
2024,
Номер
24(5), С. 1293 - 1306
Опубликована: Янв. 1, 2024
This
review
delves
into
microphysiological
systems,
miniature
physiological
environments
used
to
evaluate
biological
products,
reducing
the
need
for
animal
experimentation.
We
consider
their
benefits
as
well
persistent
challenges
in
material
selection/fabrication
and
reproducibility.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(21)
Опубликована: Март 2, 2024
Abstract
The
blood‐brain
barrier
(BBB)
is
a
highly
controlled
microenvironment
that
regulates
the
interactions
between
cerebral
blood
and
brain
tissue.
Due
to
its
selectivity,
many
therapeutics
targeting
various
neurological
disorders
are
not
able
penetrate
into
Pre‐clinical
studies
using
animals
other
in
vitro
platforms
have
shown
ability
fully
replicate
human
BBB
leading
failure
of
majority
clinical
trials.
However,
recent
innovations
ex
vivo
modeling
called
organs‐on‐chips
potential
create
more
accurate
disease
models
for
improved
drug
development.
These
microfluidic
induce
physiological
stressors
on
cultured
cells
generate
physiologically
BBBs
compared
previous
models.
In
this
review,
different
approaches
BBBs‐on‐chips
explored
alongside
their
application
therapeutic
efficacy.
Additionally,
use
delivery
discussed,
advances
linking
onto
multiorgan
mimic
organ
crosstalk
reviewed.
Frontiers in Endocrinology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 20, 2025
MODY,
or
maturity-onset
diabetes
of
the
young,
is
a
group
monogenic
diseases
characterized
by
autosomal
dominant
inheritance
non-insulin-dependent
form
that
classically
manifests
in
adolescence
young
adults
under
25
years
age.
MODY
rare
cause
diabetes,
accounting
for
1%
all
cases,
and
often
misdiagnosed
as
type
1
2
diabetes.
It
great
importance
to
accurately
diagnose
this
allows
most
appropriate
treatment
patients
facilitates
early
diagnosis
them
their
families.
This
disease
has
high
degree
phenotypic
genetic
polymorphism.
The
prevalent
forms
are
attributed
mutations
three
genes:
GCK
(MODY
2)
(HNF)1A/4A
3
1).
remaining
subtypes,
which
less
prevalent,
have
been
identified
next
generation
sequencing
(NGS)
last
decade.
Mutations
gene
result
asymptomatic,
stable
fasting
hyperglycemia,
does
not
require
specific
treatment.
HNF1A
HNF4A
genes
pancreatic
β-cell
dysfunction,
turn
causes
hyperglycemia.
leads
diabetic
angiopathy.
commonly
prescribed
drugs
hyperglycemia
sulfonylurea
derivatives.
Nevertheless,
with
advancing
age,
some
may
insulin
therapy
due
development
resistance
drugs.
strategy
still
an
experimental
approach,
it
unlikely
be
widely
used
clinic
peculiarities
structure
polymorphism
clinical
variability
even
within
same
disease.
Furthermore,
there
lack
clear
gene-phenotypic
correlations,
quite
satisfactory
curability
majority
patients.
review
presents
main
characteristics
mutation
spectrum
common
rarer
detailed
analysis
field
application
AVV
vectors
correction
resistance.
Chinese Medical Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
The
high
failure
rates
in
clinical
drug
development
based
on
animal
models
highlight
the
urgent
need
for
more
representative
human
biomedical
research.
In
response
to
this
demand,
organoids
and
organ
chips
were
integrated
greater
physiological
relevance
dynamic,
controlled
experimental
conditions.
This
innovative
platform—the
organoids-on-a-chip
technology—shows
great
promise
disease
modeling,
discovery,
personalized
medicine,
attracting
interest
from
researchers,
clinicians,
regulatory
authorities,
industry
stakeholders.
review
traces
evolution
organoids-on-a-chip,
driven
by
necessity
advanced
biological
models.
We
summarize
applications
of
simulating
pathological
phenotypes
therapeutic
evaluation
technology.
section
highlights
how
integrating
technologies
chips,
such
as
microfluidic
systems,
mechanical
stimulation,
sensor
integration,
optimizes
organoid
cell
types,
spatial
structure,
functions,
thereby
expanding
their
applications.
conclude
addressing
current
challenges
offering
insights
into
prospects.
advancement
is
poised
enhance
fidelity,
standardization,
scalability.
Furthermore,
integration
cutting-edge
interdisciplinary
collaborations
will
be
crucial
progression
Drug Metabolism and Disposition,
Год журнала:
2023,
Номер
52(3), С. 198 - 209
Опубликована: Дек. 12, 2023
Microphysiological
systems
(MPS)
are
comprised
of
one
or
multiple
cell
types
human
animal
origins
that
mimic
the
biochemical/electrical/mechanical
responses
and
blood-tissue
barrier
properties
cells
observed
within
a
complex
organ.
The
goal
incorporating
these
in
vitro
is
to
expedite
advance
drug
discovery
development
paradigm
with
improved
predictive
translational
capabilities.
Considering
industry
need
for
efficiency
broad
challenges
model
qualification
acceptance,
International
Consortium
Innovation
Quality
(IQ)
founded
an
IQ
MPS
working
group
2014
Affiliate
2018.
This
connects
thought
leaders
end
users,
provides
forum
crosspharma
collaboration,
engages
regulators
qualify
translationally
relevant
models.
To
understand
how
pharmaceutical
companies
using
MPS,
conducted
two
surveys
2019,
survey
1,
2021,
2,
which
differed
slightly
scope
definition
models
under
question.
captured
demographics,
resourcing,
rank
order
organs
interest,
compound
modalities
tested,
organ-specific
questions,
including
nonclinical
species
needs
types.
major
focus
this
manuscript
on
results
from
where
we
specifically
highlight
context
use
safety,
pharmacology,
absorption,
disposition,
metabolism,
excretion
discuss
considerations
data
regulatory
submissions.
In
summary,
provide
valuable
insights
developers,
regulators,
pharma,
offering
view
into
current
practices
future
while
highlighting
key
impacting
adoption.
SIGNIFICANCE
STATEMENT
application
microphysiological
represents
growing
area
interest
framework.
study
surveyed
20+
pharma
areas
application,
barriers
internal
These
will
tech
providers,
starting
point
assess
state
applications
along
learnings
effectively
realize
potential
as
emerging
technology.
Molecular Therapy,
Год журнала:
2024,
Номер
32(8), С. 2584 - 2603
Опубликована: Июнь 5, 2024
Systemic
administration
of
adeno-associated
virus
(AAV)
vectors
for
spinal
cord
gene
therapy
has
challenges
including
toxicity
at
high
doses
and
pre-existing
immunity
that
reduces
efficacy.
Intrathecal
(IT)
delivery
AAV
into
cerebral
fluid
can
avoid
many
issues,
although
distribution
the
vector
throughout
is
limited,
entry
to
periphery
sometimes
initiates
hepatotoxicity.
Here
we
performed
biopanning
in
non-human
primates
(NHPs)
with
an
IT
injected
AAV9
peptide
display
library.
We
identified
top
candidates
by
sequencing
inserts
DNA
isolated
from
whole
tissue,
nuclei,
or
nuclei
transgene-expressing
cells.
These
barcoded
were
pooled
compared
biodistribution
transgene
expression
liver
NHPs.
Most
displayed
increased
retention
AAV9.
Greater
spread
lumbar
thoracic
cervical
regions
was
observed
several
capsids.
Furthermore,
capsids
decreased
AAV9,
providing
a
on-target/low
off-target
biodistribution.
Finally,
tested
human
organoids
found
them
outperform
efficiency
neurons
astrocytes.
have
potential
serve
as
leading-edge
vehicles
cord-directed
therapies.
Expert Opinion on Drug Delivery,
Год журнала:
2023,
Номер
20(8), С. 1097 - 1113
Опубликована: Авг. 3, 2023
Introduction
Inhaled
gene
therapy
programs
targeting
diseases
of
the
lung
have
seen
increasing
interest
in
recent
years,
though
as
yet
no
product
has
successfully
entered
market.
Preclinical
research
to
support
such
is
critically
important
maximizing
chances
developing
successful
candidates.
Human Gene Therapy,
Год журнала:
2024,
Номер
35(5-6), С. 139 - 150
Опубликована: Фев. 22, 2024
Inherited
kidney
diseases
are
among
the
leading
causes
of
chronic
disease,
reducing
quality
life
and
resulting
in
substantial
socioeconomic
impact.
The
advent
early
genetic
testing
growing
understanding
molecular
basis
pathophysiology
these
disorders
have
opened
avenues
for
novel
treatment
strategies.
Viral
vector-based
gene
therapies
evolved
from
experimental
treatments
rare
to
potent
platforms
that
carry
intrinsic
potential
provide
a
cure
with
single
application.
Several
therapy
products
reached
market,
numbers
only
expected
increase.
Still,
none
target
inherited
diseases.
Gene
transfer
has
lagged
when
compared
other
tissue-directed
such
as
hepatic,
neuromuscular,
ocular
tissues.
Systemic
delivery
information
tackle
disease
is
challenging.
pharma
industry
taking
steps
take
on
translate
current
research
into
therapeutic
arena.
In
this
review,
we
an
overview
viral
approaches
their
potential.
We
discuss
advances
injection
routes
been
explored
enhance
toward
cells
animal
models,
how
can
fuel
development
viable
humans.
