Liver International,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 9, 2024
Gene
therapy
is
being
successfully
developed
for
the
treatment
of
several
genetic
disorders.
Various
methods
gene
transfer
have
been
to
enable
production
deficient
enzyme
or
protein.
One
most
important
adeno-associated
virus
vectors,
which
shown
be
viable
use
in
vivo
therapy.
Several
therapies
already
approved.
They
are
also
promising
acquired
diseases.
Important
examples
include
haemophilia
A
and
B,
X-linked
myotubular
myopathy,
spinal
muscular
atrophy
liver
diseases
such
as
Criggler-Najjar
disease,
alpha-1
antitrypsin
deficiency
Fabry
disease.
However,
introduction
a
foreign
compound
into
hepatocytes
leads
hepatic
reactions
with
heterogeneous
phenotypic
expression
wide
spectrum
severity,
ranging
from
mild
transaminase
elevation
acute
failure.
mechanisms
appear
involved
injury,
including
an
immune
response,
but
direct
toxicity
depending
on
method
transfer.
As
result,
incidence,
severity
injury
vary
indication
patient
patient.
Patients
treated
more
prone
than
those
B.
Corticosteroids
used
correct
prevent
degradation
transferred
loss
therapeutic
activity.
The
aim
this
review
describe
risk
according
short-
long-term
management
currently
proposed
clinical
practice.
Journal of Virology,
Год журнала:
2024,
Номер
98(6)
Опубликована: Май 22, 2024
Adeno-associated
viruses
(AAVs)
package
a
single-stranded
(ss)
DNA
genome
of
4.7
kb
in
their
capsid
~20
nm
diameter.
AAV
replication
requires
co-infection
helper
virus,
such
as
adenovirus.
During
the
optimization
recombinant
production,
small
viral
nonstructural
protein,
membrane-associated
accessory
protein
(MAAP),
was
identified.
However,
function
MAAP
context
infection
remains
unknown.
Here,
we
investigated
expression
strategy
and
during
both
AAV2
AAV5
human
embryonic
kidney
(HEK)293
cells.
We
found
that
MAAP2
MAAP5
are
expressed
from
gene
(
Nature Biotechnology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 29, 2025
Abstract
Therapeutic
efficacy
and
safety
of
adeno-associated
virus
(AAV)
liver
gene
therapy
depend
on
capsid
choice.
To
predict
AAV
performance
under
near-clinical
conditions,
we
established
side-by-side
comparison
at
single-cell
resolution
in
human
livers
maintained
by
normothermic
machine
perfusion.
AAV-LK03
transduced
hepatocytes
much
more
efficiently
specifically
than
AAV5,
AAV8
AAV6,
which
are
most
commonly
used
clinically,
AAV-NP59,
is
better
transducing
engrafted
immune-deficient
mice.
preferentially
periportal
normal
liver,
whereas
AAV5
targeted
pericentral
steatotic
liver.
sinusoidal
endothelial
cells
as
hepatocytes.
steatosis
influenced
vector
episome
formation,
determines
durability,
with
delaying
concatemerization.
Our
findings
inform
choice
clinical
therapy,
including
consideration
disease-relevant
hepatocyte
zonation
effects
steatosis,
facilitate
the
development
capsids
that
transduce
or
other
therapeutically
relevant
cell
types
maximum
efficiency
specificity.
Seminars in Thrombosis and Hemostasis,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 8, 2024
Abstract
Strides
in
advancements
of
care
persons
with
hemophilia
include
development
long-acting
factor
replacement
therapies,
novel
substitution
and
hemostatic
rebalancing
agents,
most
recently
approved
gene
therapy.
Several
decades
preclinical
clinical
trials
have
led
to
adeno-associated
viral
(AAV)
vector-mediated
transfer
for
endogenous
production
VIII
(FVIII)
A
(HA).
Only
one
therapy
product
HA
(valoctocogene
roxaparvovec)
has
been
by
regulatory
authorities.
Results
valoctocogene
roxaparvovec
trial
show
significant
improvement
bleeding
rates
use
therapy;
however,
sustainability
duration
response
variability
overall
decline
FVIII
expression
over
time.
Further
challenges
untoward
adverse
effects
involving
liver
toxicity
requiring
immunosuppression
neutralizing
antibodies
AAV
vector
rendering
future
doses
ineffective.
Real-life
applicability
will
require
appropriate
patient
screening,
infrastructure
setup,
long-term
monitoring
including
data
collection
patient-reported
outcomes
innovative
payment
schemes.
This
review
article
highlights
the
success
trials,
response,
perspectives
on
approach
shared
decision-making
need
strategies
overcome
several
unmet
needs.
Journal of Applied Genetics,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Hemophilia
B
is
a
disease
that
affects
the
human
coagulation
system,
causing
absence
or
deficiency
of
factor
IX,
which
may
manifest
itself
in
uncontrolled
bleeding
life-threatening
to
patients.
Due
its
inheritance,
more
often
men,
and
severity
symptoms
directly
correlates
with
concentration
missing
IX;
hence,
aim
therapy
maintain
it
at
level
allows
for
sufficient
hemostasis.
The
basic
model
treatment
offered
patients
based
on
primary
prevention
IX
prolonged
half-life,
which,
however,
does
not
solve
numerous
problems
faced
by
An
innovative
proposal
that,
despite
initial
concerns,
becoming
popular
every
day
recently
approved
genetic
Europe,
uses
viral
vectors
transfer
correct
gene
encodes
IX.
introduction
recombinant
place
defective
counterpart
seems
be
promising
solution
beginning
new
era
therapies
have
chance
develop
their
full
potential
replace
existing
therapeutic
regimens.
Viruses,
Год журнала:
2024,
Номер
16(8), С. 1215 - 1215
Опубликована: Июль 29, 2024
Adeno-associated
viruses
(AAVs)
are
small,
non-enveloped
that
package
a
single-stranded
(ss)DNA
genome
of
4.7
kilobases
(kb)
within
their
T
=
1
icosahedral
capsid.
AAVs
replication-deficient
require
helper
virus
to
complete
life
cycle.
Recombinant
(r)AAVs
have
been
utilized
as
gene
delivery
vectors
for
decades
in
therapy
applications.
So
far,
six
rAAV-based
medicines
approved
by
the
US
FDA.
The
kb
ssDNA
AAV
encodes
nine
proteins,
including
three
viral
structural/capsid
VP1,
VP2,
and
VP3;
four
large
nonstructural
proteins
(replication-related
proteins),
Rep78/68
Rep52/40;
two
small
proteins.
nonstructured
accessory
namely
assembly
associated
protein
(AAP)
membrane-associated
(MAAP).
Although
conserved
serotypes,
functions
largely
obscure.
In
this
review,
we
focus
on
expression
strategy
functional
properties
AAVs.
