Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Nov. 25, 2024
Polyfunctional
T
cells
programmed
to
perform
activities
such
as
degranulation
of
lytic
enzymes
and
simultaneous
production
multiple
cytokines
are
associated
with
more
effective
control
viral
infections.
Immune
responses
recombinant
adeno-associated
virus
(rAAV)
vector
delivery
systems
can
critically
influence
therapeutic
efficacy
safety
gene
therapy.
However,
knowledge
polyfunctional
in
anti-AAV
immune
is
scarce.
To
bridge
this
gap,
we
have
investigated
the
polyfunctionality
primary
human
CD4
from
healthy
donors
after
Human Gene Therapy,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 23, 2024
Adeno-associated
virus
(AAV)
vectors
have
demonstrated
safety
and
efficacy
for
gene
transfer
to
hepatocytes
in
preclinical
models,
various
clinical
trials
from
a
experience
with
growing
number
of
approved
therapy
products.
Although
the
exact
duration
is
unknown,
expression
therapeutic
genes
remains
stable
several
years
after
single
administration
vector
at
clinically
relevant
doses
adult
patients
hemophilia
other
inherited
metabolic
disorders.
However,
applications,
especially
diseases
requiring
high
AAV
by
intravenous
administrations,
raised
concerns.
These
include
prevalence
pre-existing
immunity
against
capsid,
activation
complement
innate
serious
life-threatening
complications,
elevation
liver
transaminases,
growth
associated
loss
transgene
expression,
underlying
conditions
negatively
affecting
efficacy.
Despite
these
issues,
field
rapidly
advancing
better
understanding
vector-host
interactions
development
new
strategies
improve
liver-directed
therapy.
This
review
provides
an
overview
current
emerging
challenges
AAV-mediated
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: July 10, 2024
Abstract
Adeno-associated
viruses
(AAVs)
are
promising
gene
therapy
vectors,
but
challenges
arise
when
treating
patients
with
preexisting
neutralizing
antibodies.
Worldwide
seroprevalence
studies
provide
snapshots
of
existing
immunity
in
diverse
populations.
Owing
to
the
uniqueness
Basque
socio-geographical
landscape,
we
investigated
eight
AAV
serotypes
residents
Country.
We
found
highest
AAV3,
and
lowest
AAV9.
Additionally,
less
than
50%
population
has
antibodies
against
AAV4,
AAV6,
Our
findings
insight
into
infections
region,
public
health,
development
AAV-based
therapeutics.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 11, 2024
Summary
Artificial
intelligence
(AI)
has
been
suggested
to
facilitate
time-
and
cost-effective
functional
engineering
of
adeno-associated
virus
(AAV)
capsid
sequences.
Nevertheless,
an
AI-empowered
approach
identify
AAV
sequence-to-multifunction
relationships
remains
elusive.
To
overcome
this
challenge,
we
propose
a
machine-intelligent
design
method
map
sequence
multiple
functions,
thereby
enabling
direct
in
silico
capsids.
fuse
functions
into
single
sequence,
heuristic
algorithm
coupled
with
contrastive
learning
reinforcement
learning,
named
function-guided
evolution
(FE),
was
introduced
steer
further
the
high-performing
sequences
generated
by
naïve
language
model
toward
functions.
We
then
illustrated
evolutionary
mechanism
FE
for
generation
Further
optimization
steers
desired
within
landscape.
Despite
constraint
datasets
only
129
entries,
successfully
constructed
improved
viability
central
nervous
system
(CNS)
tropism.
In
vivo
experiments
confirmed
that
two
top
eight
engineered
variants
exhibited
enhanced
remarkable
CNS
This
interpretable
represents
pioneering
effort
capsids
effective
gene
delivery.
Graph
Abstract
Brief
study
introduces
ALICE,
novel
enables
have
validated
tropism
through
ALICE.
Highlights
ALICE
Utilizing
limited
dataset
maps
elucidated
system.
revealed
exhibit
increased
about
372-fold
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Nov. 25, 2024
Polyfunctional
T
cells
programmed
to
perform
activities
such
as
degranulation
of
lytic
enzymes
and
simultaneous
production
multiple
cytokines
are
associated
with
more
effective
control
viral
infections.
Immune
responses
recombinant
adeno-associated
virus
(rAAV)
vector
delivery
systems
can
critically
influence
therapeutic
efficacy
safety
gene
therapy.
However,
knowledge
polyfunctional
in
anti-AAV
immune
is
scarce.
To
bridge
this
gap,
we
have
investigated
the
polyfunctionality
primary
human
CD4
from
healthy
donors
after
