Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: June 27, 2022
Abstract
Retinal
dystrophies
such
as
Retinitis
pigmentosa
are
among
the
most
prevalent
causes
of
inherited
legal
blindness,
for
which
treatments
in
demand.
prostheses
have
been
developed
to
stimulate
inner
retinal
network
that,
initially
spared
by
degeneration,
deteriorates
late
stages
disease.
We
recently
reported
that
conjugated
polymer
nanoparticles
persistently
rescue
visual
activities
after
a
single
subretinal
injection
Royal
College
Surgeons
rat
model
.
Here
we
demonstrate
can
reinstate
physiological
signals
at
cortical
level
and
visually
driven
when
microinjected
10-months-old
rats
bearing
fully
light-insensitive
retinas.
The
extent
restoration
positively
correlates
with
nanoparticle
density
hybrid
contacts
second-order
neurons.
results
establish
functional
role
organic
photovoltaic
restoring
degenerate
retinas
intense
retina
rewiring,
stage
disease
patients
subjected
prosthetic
interventions.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(2)
Published: Jan. 11, 2023
Lipid
nanoparticle
(LNP)-based
mRNA
delivery
holds
promise
for
the
treatment
of
inherited
retinal
degenerations.
Currently,
LNP-mediated
is
restricted
to
pigment
epithelium
(RPE)
and
Müller
glia.
LNPs
must
overcome
ocular
barriers
transfect
neuronal
cells
critical
visual
phototransduction,
photoreceptors
(PRs).
We
used
a
combinatorial
M13
bacteriophage-based
heptameric
peptide
phage
display
library
mining
ligands
that
target
PRs.
identified
most
promising
candidates
resulting
from
in
vivo
biopanning.
Dye-conjugated
peptides
showed
rapid
localization
decorated
with
top-performing
delivered
PRs,
RPE,
glia
mice.
This
distribution
translated
nonhuman
primate
eye,
wherein
robust
protein
expression
was
observed
glia,
RPE.
Overall,
we
have
developed
peptide-conjugated
can
enable
neural
retina,
expanding
utility
LNP-mRNA
therapies
blindness.
Cell,
Journal Year:
2022,
Volume and Issue:
185(4), P. 672 - 689.e23
Published: Feb. 1, 2022
ChRmine,
a
recently
discovered
pump-like
cation-conducting
channelrhodopsin,
exhibits
puzzling
properties
(large
photocurrents,
red-shifted
spectrum,
and
extreme
light
sensitivity)
that
have
created
new
opportunities
in
optogenetics.
ChRmine
its
homologs
function
as
ion
channels
but,
by
primary
sequence,
more
closely
resemble
pump
rhodopsins;
mechanisms
for
passive
channel
conduction
this
family
remained
mysterious.
Here,
we
present
the
2.0
Å
resolution
cryo-EM
structure
of
revealing
architectural
features
atypical
channelrhodopsins:
trimeric
assembly,
short
transmembrane-helix
3,
twisting
extracellular-loop
1,
large
vestibules
within
monomer,
an
opening
at
trimer
interface.
We
applied
to
design
three
proteins
(rsChRmine
hsChRmine,
conferring
further
high-speed
properties,
respectively,
frChRmine,
combining
faster
performance)
suitable
fundamental
neuroscience
opportunities.
These
results
illuminate
gating
channelrhodopsins
point
way
toward
structure-guided
creation
applications
across
biology.
Annual Review of Neuroscience,
Journal Year:
2022,
Volume and Issue:
45(1), P. 447 - 469
Published: April 20, 2022
Recombinant
adeno-associated
viruses
(AAVs)
are
commonly
used
gene
delivery
vehicles
for
neuroscience
research.
They
have
two
engineerable
features:
the
capsid
(outer
protein
shell)
and
cargo
(encapsulated
genome).
These
features
can
be
modified
to
enhance
cell
type
or
tissue
tropism
control
transgene
expression,
respectively.
Several
engineered
AAV
capsids
with
unique
tropisms
been
identified,
including
variants
enhanced
central
nervous
system
transduction,
specificity,
retrograde
transport
in
neurons.
Pairing
these
AAVs
modern
regulatory
elements
state-of-the-art
reporter,
sensor,
effector
enables
highly
specific
expression
anatomical
functional
analyses
of
brain
cells
circuits.
Here,
we
discuss
recent
advances
that
provide
a
comprehensive
(capsid
cargo)
toolkit
genetic
access
molecularly
defined
types.
Science,
Journal Year:
2023,
Volume and Issue:
381(6665)
Published: Sept. 28, 2023
Systemic
metabolism
has
to
be
constantly
adjusted
the
variance
of
food
intake
and
even
prepared
for
anticipated
changes
in
nutrient
availability.
Therefore,
brain
integrates
multiple
homeostatic
signals
with
numerous
cues
that
predict
future
deviations
energy
supply.
Recently,
our
understanding
neural
pathways
underlying
these
regulatory
principles-as
well
as
their
convergence
hypothalamus
key
coordinator
intake,
expenditure,
glucose
metabolism-have
been
revealed.
These
advances
have
changed
view
brain-dependent
control
metabolic
physiology.
In
this
Review,
we
discuss
new
concepts
about
how
alterations
contribute
development
prevalent
diseases
such
obesity
type
2
diabetes
mellitus
emerging
knowledge
may
provide
targets
treatment.
Physiological Reviews,
Journal Year:
2022,
Volume and Issue:
102(3), P. 1263 - 1325
Published: Jan. 24, 2022
Optogenetics
combines
light
and
genetics
to
enable
precise
control
of
living
cells,
tissues,
organisms
with
tailored
functions.
has
the
advantages
noninvasiveness,
rapid
responsiveness,
tunable
reversibility,
superior
spatiotemporal
resolution.
Following
initial
discovery
microbial
opsins
as
light-actuated
ion
channels,
a
plethora
naturally
occurring
or
engineered
photoreceptors
photosensitive
domains
that
respond
at
varying
wavelengths
ushered
in
next
chapter
optogenetics.
Through
protein
engineering
synthetic
biology
approaches,
genetically
encoded
photoswitches
can
be
modularly
into
scaffolds
host
cells
myriad
biological
processes,
well
behavioral
disease
intervention
vivo.
Here,
we
summarize
these
optogenetic
tools
on
basis
their
fundamental
photochemical
properties
better
inform
chemical
design
principles.
We
also
highlight
exemplary
applications
opsin-free
optogenetics
dissecting
cellular
physiology
(designated
"optophysiology")
describe
current
progress,
future
trends,
wireless
optogenetics,
which
enables
remote
interrogation
physiological
processes
minimal
invasiveness.
This
review
is
anticipated
spark
novel
thoughts
next-generation
devices
promise
accelerate
both
basic
translational
studies.
