International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(24), С. 13540 - 13540
Опубликована: Дек. 18, 2024
Gene
transfection
is
a
fundamental
technique
in
the
fields
of
biological
research
and
therapeutic
innovation.
Due
to
their
biocompatibility
membrane-mimetic
properties,
lipid
vectors
serve
as
essential
tools
transfection.
The
successful
delivery
genetic
material
into
cytoplasm
contingent
upon
fusion
vector
cellular
membranes,
which
enables
hydrophilic
polynucleic
acids
traverse
hydrophobic
barriers
two
intervening
membranes.
This
review
examines
critical
role
membrane
lipofection
efficiency,
with
particular
focus
on
molecular
mechanisms
that
govern
lipoplex–membrane
interactions.
analysis
will
examine
key
challenges
inherent
process,
from
achieving
initial
proximity
facilitating
final
content
release
through
remodeling.
In
contrast
viral
vectors,
utilize
specialized
proteins,
necessitate
strategic
formulation
environmental
optimization
enhance
fusogenicity.
discusses
recent
advances
design
fusion-promoting
strategies,
emphasizing
potential
improve
gene
yield.
It
highlights
importance
understanding
for
developing
next-generation
systems
emphasizes
need
continued
advance
lipid-mediated
technology.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
Intranasal
delivery
of
mRNA
vaccines
offers
promising
opportunities
to
combat
airborne
viruses
like
SARS‐CoV‐2
by
provoking
mucosal
immunity,
which
not
only
defends
against
respiratory
infection
but
also
prevents
contagious
transmission.
However,
the
development
nasal
has
been
hampered
lack
effective
means
overcome
mucus
barrier.
Herein,
ionizable
lipid‐incorporated
liquid
lipid
nanoparticles
(iLLNs)
capable
delivering
cargo
across
airway
mucosa
are
designed.
Adjusting
ratios
and
cationic
lipids
allows
fine‐tuning
p
K
a
iLLNs
range
pH
(5.5–6.5),
thus
facilitating
penetration
via
formation
near‐neutral,
PEGylated
muco‐inert
surfaces.
When
nasally
administered
mice,
top
candidate
iLLN‐2/mRNA
complexes
enable
about
60‐fold
greater
reporter
gene
expression
in
cavity,
compared
benchmark
mRNA‐lipid
(ALC‐LNP)
having
same
composition
as
that
BNT162b2
vaccine.
Moreover,
prime‐boost
intranasal
immunization
elicits
magnitude
spike‐specific
IgA
IgG
response
than
ALC‐LNP,
without
triggering
any
noticeable
inflammatory
reactions.
Taken
together,
these
results
provide
useful
insights
for
design
deliverable
formulations
prophylactic
applications.
In
the
past
10
years,
CRISPR-Cas9
has
revolutionized
gene-editing
field
due
to
its
modularity,
simplicity,
and
efficacy.
It
been
applied
for
creation
of
in
vivo
models,
further
understand
human
biology,
toward
curing
genetic
diseases.
However,
there
remain
significant
delivery
barriers
application
clinic,
especially
extrahepatic
applications.
this
work,
high-throughput
molecular
barcoding
techniques
were
used
alongside
traditional
screening
methodologies
simultaneously
evaluate
LNP
formulations
encapsulating
ribonucleoproteins
(RNPs)
vitro
efficiency
biodistribution.
This
resulted
identification
a
lung-tropic
formulation,
which
shows
efficient
gene
editing
endothelial
epithelial
cells
within
lung,
targeting
both
model
reporter
clinically
relevant
genomic
targets.
Further,
no
off-target
indel
formation
liver,
making
it
highly
specific
system
lung-editing
