Journal of Inherited Metabolic Disease,
Journal Year:
2024,
Volume and Issue:
47(1), P. 176 - 191
Published: Jan. 1, 2024
Abstract
Inborn
errors
of
neurotransmitter
(NT)
metabolism
are
a
group
rare,
heterogenous
diseases
with
predominant
neurological
features,
such
as
movement
disorders,
autonomic
dysfunction,
and
developmental
delay.
Clinical
overlap
other
disorders
has
led
to
delayed
diagnosis
treatment,
some
conditions
refractory
oral
pharmacotherapies.
Gene
therapies
have
been
developed
translated
clinics
for
paediatric
inborn
metabolism,
38
interventional
clinical
trials
ongoing
date.
Furthermore,
efforts
in
restoring
dopamine
synthesis
neurotransmission
through
viral
gene
therapy
Parkinson's
disease.
Along
the
recent
European
Medicines
Agency
(EMA)
Healthcare
Products
Regulatory
(MHRA)
approval
an
AAV2
supplementation
AADC
deficiency,
promising
efficacy
safety
profiles
can
be
achieved
this
diseases.
In
review,
we
present
preclinical
advances
address
NT‐related
diseases,
summarise
potential
challenges
that
require
careful
considerations
NT
studies.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: April 2, 2024
Abstract
Adeno-associated
virus
(AAV)
has
emerged
as
a
pivotal
delivery
tool
in
clinical
gene
therapy
owing
to
its
minimal
pathogenicity
and
ability
establish
long-term
expression
different
tissues.
Recombinant
AAV
(rAAV)
been
engineered
for
enhanced
specificity
developed
treating
various
diseases.
However,
rAAV
is
being
more
widely
used
therapy,
the
increased
demand
created
challenges
existing
manufacturing
methods.
Seven
rAAV-based
products
have
received
regulatory
approval,
but
there
continue
be
concerns
about
safely
using
high-dose
viral
therapies
humans,
including
immune
responses
adverse
effects
such
genotoxicity,
hepatotoxicity,
thrombotic
microangiopathy,
neurotoxicity.
In
this
review,
we
explore
biology
with
an
emphasis
on
current
vector
engineering
strategies
technologies.
We
discuss
how
rAAVs
are
employed
ongoing
trials
ocular,
neurological,
metabolic,
hematological,
neuromuscular,
cardiovascular
diseases
well
cancers.
outline
triggered
by
rAAV,
address
associated
side
effects,
mitigate
these
reactions.
hope
that
discussing
recent
advancements
field
will
helpful
guide
researchers
clinicians
navigating
ever-evolving
landscape
of
therapy.
Frontiers in Bioengineering and Biotechnology,
Journal Year:
2022,
Volume and Issue:
10
Published: May 12, 2022
The
Clustered
Regularly
Interspaced
Short
Palindromic
Repeat
(CRISPR)
and
its
accompanying
protein
(Cas9)
are
now
the
most
effective,
efficient,
precise
genome
editing
techniques.
Two
essential
components
of
CRISPR/Cas9
system
guide
RNA
(gRNA)
CRISPR-associated
proteins.
Choosing
implementing
safe
effective
delivery
systems
in
therapeutic
application
has
proven
to
be
a
significant
problem.
For
vivo
delivery,
viral
vectors
natural
specialists.
Due
their
higher
effectiveness
than
other
methods,
such
as
adenoviral
(AdVs),
adeno-associated
viruses
(AAVs),
lentivirus
(LVs)
commonly
employed
methods.
This
review
thoroughly
examined
recent
achievements
using
variety
means
well
benefits
limitations
each
vector.
Future
thoughts
for
overcoming
current
restrictions
adapting
technology
also
discussed.
Molecular Therapy,
Journal Year:
2023,
Volume and Issue:
31(6), P. 1533 - 1549
Published: Jan. 7, 2023
RNA
therapeutics
have
had
a
tremendous
impact
on
medicine,
recently
exemplified
by
the
rapid
development
and
deployment
of
mRNA
vaccines
to
combat
COVID-19
pandemic.
In
addition,
RNA-targeting
drugs
been
developed
for
diseases
with
significant
unmet
medical
needs
through
selective
knockdown
or
modulation
pre-mRNA
splicing.
Recently,
editing,
particularly
antisense
RNA-guided
adenosine
deaminase
acting
(ADAR)-based
programmable
A-to-I
has
emerged
as
powerful
tool
manipulate
enable
correction
disease-causing
mutations
modulate
gene
expression
protein
function.
Beyond
correcting
pathogenic
mutations,
technology
is
well
suited
therapeutic
applications
that
require
transient
pharmacodynamic
effect,
such
treatment
acute
pain,
obesity,
viral
infection,
inflammation,
where
it
would
be
undesirable
introduce
permanent
alterations
genome.
Furthermore,
function,
altering
active
sites
enzymes
interface
protein-protein
interactions,
opens
door
avenues
ranging
from
regenerative
medicine
oncology.
These
emerging
RNA-editing-based
toolsets
are
poised
broadly
biotechnology
applications.
Here,
we
review
field
highlight
recent
laboratory
advancements,
discuss
key
challenges
path
clinical
development.
Molecules,
Journal Year:
2023,
Volume and Issue:
28(3), P. 1498 - 1498
Published: Feb. 3, 2023
Breast
cancer
incidence
and
mortality
rates
have
increased
exponentially
during
the
last
decade,
particularly
among
female
patients.
Current
therapies,
including
surgery
chemotherapy,
significant
negative
physical
mental
impacts
on
As
a
safer
alternative,
gene
therapy
utilising
therapeutic
with
potential
to
treat
various
ailments
is
being
considered.
Delivery
of
generally
utilises
viral
vectors.
However,
immunological
reactions
even
been
recorded
as
side
effects.
result,
non-viral
vectors,
such
liposomes,
system
composed
lipid
bilayers
formed
into
nanoparticles,
are
studied.
Liposomes
demonstrated
tremendous
due
their
limitless
ability
combine
many
functions
desirable
characteristics
functionality.
This
article
discusses
cationic,
anionic,
neutral
liposomes
stability,
cytotoxicity,
transfection
ability,
cellular
uptake,
limitation
carrier
suitable
for
specifically
cancer.
Due
more
practical
approach
employing
electrostatic
contact
negatively
charged
nucleic
acid
cell
membrane
absorption
purposes,
cationic
appear
be
suited
formulation
delivery
breast
treatment.
other
alternatives
numerous
complicated
additional
modifications,
attachments
need
made
achieve
functional
treatment,
which
were
also
discussed
in
this
review.
review
aimed
increase
understanding
build
viable
treatment
strategy.
Gene Therapy,
Journal Year:
2023,
Volume and Issue:
30(10-11), P. 738 - 746
Published: Nov. 1, 2023
Despite
the
ups
and
downs
in
field
over
three
decades,
science
of
gene
therapy
has
continued
to
advance
provide
enduring
treatments
for
increasing
number
diseases.
There
are
active
clinical
trials
approaching
a
variety
inherited
acquired
disorders
different
organ
systems.
Approaches
include
ex
vivo
modification
hematologic
stem
cells
(HSC),
T
lymphocytes
other
immune
cells,
as
well
delivery
genes
or
editing
reagents
relevant
target
by
either
local
systemic
administration.
In
this
article,
we
highlight
success
ongoing
challenges
areas
high
activity
therapy:
blood
cell
diseases
targeting
hematopoietic
malignant
using
effector
genetically
modified
with
chimeric
antigen
receptors,
ophthalmologic,
neurologic,
coagulation
administration
adeno-associated
virus
(AAV)
vectors.
recent
years,
there
have
been
true
cures
many
these
diseases,
sustained
benefit
that
exceed
those
from
medical
approaches.
Each
faces
challenges,
namely
their
one-time
costs
complexity
manufacturing
therapeutic
agents,
which
biological
viruses
products,
at
pharmacologic
standards
quality
consistency.
New
models
reimbursement
needed
make
innovative
widely
available
patients
need.
Investigative Ophthalmology & Visual Science,
Journal Year:
2023,
Volume and Issue:
64(7), P. 39 - 39
Published: June 30, 2023
Since
long
before
the
first
approval
of
gene
therapy
for
retinal
disease,
ocular
has
captured
hopes
patients,
clinicians,
and
scientists
alike.
Indeed,
retina
provides
a
unique
system
studying
treating
diseases,
it
holds
distinction
as
tissue
targeted
by
an
approved
inherited
disorders
in
United
States.
There
are
many
methods
addressing
genetic
diseases
eyes
using
wide
range
potential
delivery
systems
vectors.
However,
despite
immense
progress
over
last
several
decades,
both
old
new
challenges
remain,
such
long-term
effects
treatments,
immunogenicity,
targeting,
manufacturing.
This
review
discussion
history
therapy,
various
approaches,
to
deliver
directly
tissues
(including
routes
administration
vectors),
current
clinical
trial
landscape,
future
directions
field.
Biotechnology and Bioengineering,
Journal Year:
2023,
Volume and Issue:
120(9), P. 2601 - 2621
Published: May 1, 2023
Abstract
Gene
therapy
is
a
promising
therapeutic
approach
for
genetic
and
acquired
diseases
nowadays.
Among
DNA
delivery
vectors,
recombinant
adeno‐associated
virus
(rAAV)
one
of
the
most
effective
safest
vectors
used
in
commercial
drugs
clinical
trials.
However,
current
yield
rAAV
biomanufacturing
lags
behind
necessary
dosages
use,
which
embodies
concentrated
reflection
low
productivity
from
host
cells,
difficult
scalability
rAAV‐producing
bioprocess,
high
levels
impurities
materialized
during
production.
Those
issues
directly
impact
price
gene
medicine
market,
limiting
patients’
access
to
therapy.
In
this
context,
practices
several
critical
challenges
associated
with
bioprocesses
are
reviewed,
followed
by
discussion
recent
advances
rAAV‐mediated
other
biological
fields
that
could
improve
if
these
integrated
effectively
into
systems.
This
review
aims
provide
state‐of‐the‐art
technology
perspectives
enhance
while
reducing
production
rAAV.
Frontiers in Oncology,
Journal Year:
2024,
Volume and Issue:
14
Published: April 10, 2024
Cancer
is
a
severe
disease
that
results
in
death
all
countries
of
the
world.
A
nano-based
drug
delivery
approach
best
alternative,
directly
targeting
cancer
tumor
cells
with
improved
cellular
uptake.
Different
types
nanoparticle-based
carriers
are
advanced
for
treatment
cancer,
and
to
increase
therapeutic
effectiveness
safety
therapy,
many
substances
have
been
looked
into
as
carriers.
Lipid-based
nanoparticles
(LBNPs)
significantly
attracted
interest
recently.
These
natural
biomolecules
alternate
other
polymers
frequently
recycled
medicine
due
their
amphipathic
properties.
Lipid
typically
provide
variety
benefits,
including
biocompatibility
biodegradability.
This
review
covers
different
classes
LBNPs,
characterization
synthesis
technologies.
discusses
most
significant
advancements
lipid
nanoparticle
technology
use
administration.
Moreover,
also
emphasized
applications
used
types.
