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.
Advanced Materials,
Год журнала:
2024,
Номер
36(31)
Опубликована: Июнь 6, 2024
Abstract
The
recent
success
of
gene
therapy
during
the
COVID‐19
pandemic
has
underscored
importance
effective
and
safe
delivery
systems.
Complementing
lipid‐based
systems,
polymers
present
a
promising
alternative
for
delivery.
Significant
advances
have
been
made
in
past,
with
multiple
clinical
trials
progressing
beyond
phase
I
several
companies
actively
working
on
polymeric
systems
which
provides
assurance
that
carriers
can
soon
achieve
translation.
massive
advantage
structural
tunability
vast
chemical
space
is
being
leveraged
to
mitigate
shortcomings
traditional
polycationic
improve
translatability
Tailored
approaches
diverse
nucleic
acids
specific
subcellular
targets
are
now
designed
therapeutic
efficacy.
This
review
describes
polymer
design
improved
by
polyplexes
covalent
polymer‐nucleic
acid
conjugates.
also
offers
brief
note
novel
computational
techniques
design.
concludes
an
overview
current
state
therapies
clinic
as
well
future
directions
their
translation
clinic.
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.
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.
