Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights
Viruses,
Год журнала:
2024,
Номер
16(3), С. 442 - 442
Опубликована: Март 12, 2024
Today,
adeno-associated
virus
(AAV)-based
vectors
are
arguably
the
most
promising
in
vivo
gene
delivery
vehicles
for
durable
therapeutic
expression.
Advances
molecular
engineering,
high-throughput
screening
platforms,
and
computational
techniques
have
resulted
a
toolbox
of
capsid
variants
with
enhanced
performance
over
parental
serotypes.
Despite
their
considerable
promise
emerging
clinical
success,
there
still
obstacles
hindering
broader
use,
including
limited
transduction
capabilities,
tissue/cell
type-specific
tropism
penetration
into
tissues
through
anatomical
barriers,
off-target
tissue
biodistribution,
intracellular
degradation,
immune
recognition,
lack
translatability
from
preclinical
models
to
settings.
Here,
we
first
describe
mechanisms
natural
AAV
serotypes
explore
current
understanding
systemic
cellular
hurdles
efficient
transduction.
We
then
outline
progress
developing
designer
variants,
highlighting
seminal
discoveries
which
can
transduce
central
nervous
system
upon
administration,
and,
lesser
extent,
discuss
targeting
peripheral
system,
eye,
ear,
lung,
liver,
heart,
skeletal
muscle,
emphasizing
cell
specificity
translational
promise.
In
particular,
dive
deeper
behind
properties,
focus
on
engagement
host
receptors
previously
inaccessible
Finally,
summarize
main
findings
our
review
future
directions.
Язык: Английский
Emerging trends in virus and virus-like particle gene therapy delivery to the brain
Molecular Therapy — Nucleic Acids,
Год журнала:
2024,
Номер
35(3), С. 102280 - 102280
Опубликована: Июль 20, 2024
Recent
advances
in
gene
therapy
and
gene-editing
techniques
offer
the
very
real
potential
for
successful
treatment
of
neurological
diseases.
However,
drug
delivery
constraints
continue
to
impede
viable
therapeutic
interventions
targeting
brain
due
its
anatomical
complexity
highly
restrictive
microvasculature
that
is
impervious
many
molecules.
Realizing
gene-based
therapies
requires
robust
encapsulation
safe
efficient
target
cells.
Although
viral
vectors
have
been
widely
used
targeted
therapies,
drawbacks
such
as
host
genome
integration,
prolonged
expression,
undesired
off-target
mutations,
immunogenicity
led
development
alternative
strategies.
Engineered
virus-like
particles
(eVLPs)
are
an
emerging,
promising
platform
can
be
engineered
achieve
neurotropism
through
pseudotyping.
This
review
outlines
strategies
improve
eVLP
agents.
Язык: Английский
Optimized AAV capsids for diseases of the basal ganglia show robust potency and distribution in adult nonhuman primates
DE Leib,
YH Chen,
Luis Tecedor
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 5, 2024
Abstract
Huntington’s
disease
and
other
disorders
of
the
basal
ganglia
create
challenges
for
biomolecule-based
medicines
given
poor
accessibility
these
deep
brain
structures
following
intracerebral
or
intravascular
delivery.
Additionally,
adeno-associated
viruses
(AAVs)
delivery
exposes
peripheral
tissues
to
vast
majority
therapy,
increasing
risk
immune
responses
quantity
associated
cost
goods
required
therapeutically
relevant
penetration
levels.
Here,
we
found
that
low
dose,
volume
unbiased
AAV
libraries
into
a
focused
region
allowed
recovery
novel
capsids
capable
broad
access
key
cortical
human
therapies
at
doses
orders
magnitude
lower
than
used
in
current
clinical
trials.
One
such
capsid,
AAV-DB-3,
provided
transduction
up
45%
medium
spiny
neurons
adult
NHP
striatum,
along
with
substantial
layer
cortex.
Notably,
AAV-DB-3
behaved
similarly
mice
as
NHPs
also
potently
transduced
derived
from
induced
pluripotent
stem
cells.
Thus,
provides
unique
network
level
gene
translates
down
evolutionary
scale
preclinical
studies
eventual
use.
Язык: Английский
MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(23), С. 12883 - 12883
Опубликована: Ноя. 29, 2024
MicroRNAs
(miRNAs)
maintain
cellular
homeostasis
by
blocking
mRNAs
binding
with
them
to
fine-tune
the
expression
of
genes
across
numerous
biological
pathways.
The
2024
Nobel
Prize
in
Medicine
and
Physiology
for
discovering
miRNAs
was
long
overdue.
We
anticipate
a
deluge
research
work
involving
repeat
history
prizes
awarded
on
other
RNAs.
Although
miRNA
therapies
are
included
several
complex
diseases,
realization
that
regulate
their
roles
addressing
hundreds
diseases
expected;
but
advancement
drug
discovery
tools,
we
even
faster
entry
new
drugs.
To
promote
this,
provide
details
current
science,
logic,
intellectual
property,
formulations,
regulatory
process
anticipation
many
more
researchers
will
introduce
novel
based
discussion
advice
provided
this
paper.
Язык: Английский