Brain
endothelial
cells
are
critical
for
homeostasis
of
the
central
nervous
system.
Novel
adeno-associated
viruses
(AAV)
with
brain
cell
tropism
have
been
developed
and
beginning
to
be
employed
in
mechanistic
therapeutic
research.
Studies
using
AAVs
can
involved
terms
cost,
time
personnel,
many
groups,
including
our
own,
not
experts
on
technology.
Therefore,
it
is
important
report
data
research
community
as
a
guide
ongoing
future
studies.
Here,
we
detail
initial
experience
two
most
prevalent
cells,
AAV-BR1
AAV-BI30.
One
long-term
goals
express
key
proteins
determine
impact
function.
For
method
development,
administered
AAV-BI30
CMV-driven
fluorescent
reporter
(CMV-P2A-mCherry)
wild-type
mice
intravenously
(retro-orbital)
measured
expression
peripheral
tissues
by
RT-PCR
immunostaining.
We
found
that
transduces
neurons
brain,
lung
liver,
whereas
tissue.
Our
highlights
importance
AAV
best
suited
scientific
question.
Mammalian Genome,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 13, 2025
Genome
editing,
in
particular
the
CRISPR/Cas9
system,
is
widely
used
to
generate
new
animal
models.
However,
generation
of
mutations,
such
as
conditional
knock-out
or
knock-in,
can
remain
complex
and
inefficient,
because
difficulty
deliver
donor
DNA
(single
double
stranded)
into
nucleus
fertilized
oocytes.
The
use
recombinant
adeno-associated
viruses
(rAAV)
a
rapidly
developing
approach
that
promises
improve
efficiency
creation
In
this
mini-review,
we
explore
progress
challenges
using
combination
with
rAAV
for
precise
genome
editing.
We
will
summarise
current
knowledge
transduction,
data
on
its
rodent
embryos
easily
sequence
replacements
insertions,
limitations
unexpected
events
observed
date,
protocol
optimisations
already
place
facilitate
Molecular Therapy — Nucleic Acids,
Год журнала:
2025,
Номер
36(2), С. 102495 - 102495
Опубликована: Фев. 22, 2025
Nanoblades
are
viral
particles
loaded
with
the
Cas9
protein
complexed
gRNA,
which
allowed
efficient
gene
editing
in
hematopoietic
stem
and
progenitor
cells
(HSPCs).
Combined
recombinant
adeno-associated
vector
(rAAV)
6
containing
two
homologous
arms
to
a
locus
resulted
50%
of
expression
cassette
knockin
into
HSPCs.
However,
high
effective
doses
rAAV6
induced
HSPC
cell
death.
Here,
we
demonstrated
that,
at
doses,
rAAV2
was
much
less
toxic
for
template
DNA
delivery
transduction
levels
HSPCs
equivalent
rAAV6.
To
improve
donor
delivery,
were
chemically
bio-conjugated
mannose
ligand,
via
lysine
or
tyrosine
amino
acid
residues
exposed
(AAV)
capsid
surface.
High-level
mannose-coupled
vectors
accompanied
by
remarkable
lower
toxicity
achieved
as
compared
control
correlation
highly
reduced
p53
pathway
activation.
Mannose-conjugated
combined
nanoblades
increased
survival
from
10%
80%
unmodified
even
most
immature
CD34+CD38lowCD90+
(HSC)
population.
Summarizing,
mannose-conjugated
maintained
high-level
mediated
when
without
inducing
significant
HSPCs,
an
important
feature
clinical
translation
gene-editing
strategies.
Frontiers in Medicine,
Год журнала:
2025,
Номер
12
Опубликована: Апрель 4, 2025
Introduction
Goat-derived
adeno-associated
virus
(AAV)
vectors,
such
as
AAV
Go.1,
represent
a
novel
platform
for
gene
therapy
due
to
their
unique
origin
and
potential
advantages
in
transduction
efficiency
immune
evasion.
However,
therapeutic
biological
properties
remain
underexplored.
Methods
In
this
study,
we
developed
recombinant
(rAAV)
Go.1
by
replacing
the
goat
rep
with
standard
AAV2-rep
improve
packaging
efficiency.
We
compared
of
rAAV
that
AAV5,
closely
related
serotype
95%
genome
similarity,
both
vitro
vivo
.
Additionally,
assessed
evasion
evaluating
resistance
neutralization
using
sera
from
rAAV5-immunized
mice
human
volunteers.
To
further
enhance
efficiency,
introduced
site-specific
mutations
VP1
(VP1u)
region
VP1/2
common
region.
Results
The
modification
led
significantly
higher
original
AAV.
exhibited
markedly
than
AAV5
models.
Furthermore,
demonstrated
4-fold
increase
mice.
A
study
involving
20
healthy
volunteers
revealed
high-titer
neutralizing
antibodies
had
more
pronounced
inhibitory
effect
on
rAAV5
Go.1.
Mutagenesis
studies
identified
key
modifications
enhanced
viral
properties:
K32R,
K91R,
K122R
VP1u
improved
production,
while
K137R
Discussion
Our
findings
highlight
an
vector
superior
optimize
properties,
making
promising
candidate
future
applications.
Gene
therapy
as
a
disease-modifying
therapeutic
approach
for
neurodegenerative
diseases,
such
Alzheimer's
disease
(AD)
and
Parkinson's
(PD),
is
promising
avenue.
Promising
results
in
the
preclinical
studies
involving
rodents
nonhuman
primates
utilizing
gene
have
led
to
multiple
clinical
trials
evaluating
various
genes
of
interest
AD
PD.
In
AD,
are
assessing
brain-derived
neurotrophic
factor
(BDNF)
other
targets
apolipoprotein
E2
(APOE2)
human
telomerase
reverse
transcriptase
(hTERT).
PD,
delivering
factors,
glial
cell
line-derived
(GDNF).
Additionally,
enzymes
aromatic
L-amino
acid
decarboxylase
(AADC)
glutamic
(GAD)
also
being
evaluated
All
these
primarily
utilized
adeno-associated
virus
(AAV)
deliver
above
transgene
interest.
This
review
summarizes
current
It
discusses
challenges
opportunities
associated
with
PD
ongoing
developments
related
increasing
safety
efficacy
long-term
outcomes,
which
include
evaluation
serotypes
administration
routes.
comprehensive
emphasizes
translating
findings
into
trials,
further
directions,
potential
this
alleviate
disease.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(6), С. 763 - 763
Опубликована: Июнь 11, 2024
Prime
editing
shows
potential
as
a
precision
genome
technology,
well
the
to
advance
development
of
next-generation
nanomedicine
for
addressing
neurological
disorders.
However,
turning
in
prime
editors
(PEs),
which
are
macromolecular
complexes
composed
CRISPR/Cas9
nickase
fused
with
reverse
transcriptase
and
guide
RNA
(pegRNA),
brain
remains
considerable
challenge
due
physiological
obstacles,
including
blood–brain
barrier
(BBB).
This
review
article
offers
an
up-to-date
overview
perspective
on
latest
technologies
strategies
delivery
PEs
passage
through
blood
barriers.
Furthermore,
it
delves
into
scientific
significance
possible
therapeutic
applications
conditions
related
diseases.
It
is
targeted
at
clinicians
clinical
researchers
working
advancing
neuropathologies.
Biomacromolecules,
Год журнала:
2024,
Номер
25(9), С. 5729 - 5744
Опубликована: Авг. 26, 2024
Nucleic
acid
(NA)-based
therapies
are
revolutionizing
biomedical
research
through
their
ability
to
control
cellular
functions
at
the
genetic
level.
This
work
demonstrates
a
versatile
elastin-like
polypeptide
(ELP)
carrier
system
using
layer-by-layer
(LbL)
formulation
approach
that
delivers
NA
cargos
ranging
in
size
from
siRNA
plasmids.
The
components
of
can
be
reconfigured
modulate
biochemical
and
biophysical
characteristics
for
engaging
unique
features
biological
target.
We
show
physical
characterization
performance
LbL
ELP
nucleic
nanoparticles
(LENNs)
murine
human
bladder
tumor
cell
lines.
Targeting
tumors
is
difficult
owing
constant
influx
urine
into
bladder,
leading
low
contact
times
(typically
<2
h)
therapeutic
agents
delivered
via
intravesical
instillation.
LENN
complexes
bind
cells
within
30
min
become
rapidly
internalized
release
cargo
60
min.
Our
data
readily
adaptable
NA-delivery
has
been
created
flexible
its
targeting
ability,
size,
disassembly
kinetics.
provides
an
alternative
path
either
lipid
nanoparticle
formulations
suffer
inefficiency
physicochemical
instability
or
viral
vectors
plagued
by
manufacturing
immune
rejection
challenges.
agile
ELP-based
nanocarrier
route
delivery
biomanufacturable,
biodegradable,
biocompatible,
highly
tunable
vehicle
capable
engagement
with
overexpressed
surface
receptors.
