Molecular Therapy — Methods & Clinical Development,
Год журнала:
2020,
Номер
18, С. 532 - 557
Опубликована: Июль 4, 2020
We
present
an
overview
of
clinical
trials
involving
gene
editing
using
clustered
interspaced
short
palindromic
repeats
(CRISPR)-CRISPR-associated
protein
9
(Cas9),
transcription
activator-like
effector
nucleases
(TALENs),
or
zinc
finger
(ZFNs)
and
discuss
the
underlying
mechanisms.
In
cancer
immunotherapy,
is
applied
ex
vivo
in
T
cells,
transgenic
cell
receptor
(tTCR)-T
chimeric
antigen
(CAR)-T
cells
to
improve
adoptive
therapy
for
multiple
types.
This
involves
knockouts
immune
checkpoint
regulators
such
as
PD-1,
components
endogenous
TCR
histocompatibility
leukocyte
(HLA)
complex
generate
universal
allogeneic
CAR-T
CD7
prevent
self-destruction
therapy.
cervix
carcinoma
caused
by
human
papillomavirus
(HPV),
E6
E7
genes
are
disrupted
topically
machinery.
HIV
infection,
CCR5
co-receptor
HIV-resistant
hematopoietic
stem
cells.
β-thalassemia
sickle
disease,
engineered
induce
production
fetal
hemoglobin.
AAV-mediated
exploit
liver
systemic
therapeutic
proteins
hemophilia
mucopolysaccharidoses,
eye
restore
splicing
CEP920
Leber's
congenital
amaurosis.
Close
consideration
safety
aspects
education
stakeholders
will
be
essential
a
successful
implementation
technology
clinic.
New England Journal of Medicine,
Год журнала:
2019,
Номер
381(6), С. 509 - 519
Опубликована: Июнь 14, 2019
Deoxygenated
sickle
hemoglobin
(HbS)
polymerization
drives
the
pathophysiology
of
cell
disease.
Therefore,
direct
inhibition
HbS
has
potential
to
favorably
modify
disease
outcomes.
Voxelotor
is
an
inhibitor.
mAbs,
Год журнала:
2018,
Номер
11(2), С. 219 - 238
Опубликована: Дек. 5, 2018
For
the
past
10
years,
annual
'Antibodies
to
watch'
articles
have
provided
updates
on
key
events
in
late-stage
development
of
antibody
therapeutics,
such
as
first
regulatory
review
or
approval,
that
occurred
year
before
publication
were
anticipated
occur
during
publication.
To
commemorate
10th
anniversary
article
series
and
celebrate
2018
Nobel
Prizes
Chemistry
Physiology
Medicine,
which
given
for
work
is
highly
relevant
therapeutics
research
development,
we
expanded
scope
data
presented
include
an
overview
all
commercial
clinical
approval
success
rates
this
class
molecules.
Our
indicate
that:
1)
are
entering
study,
being
approved,
record
numbers;
2)
pipeline
robust,
with
over
570
at
various
phases,
including
62
studies;
3)
Phase
1
favorable,
ranging
from
17-25%,
depending
therapeutic
area
(cancer
vs.
non-cancer).
In
2018,
a
number
(12)
antibodies
(erenumab
(Aimovig),
fremanezumab
(Ajovy),
galcanezumab
(Emgality),
burosumab
(Crysvita),
lanadelumab
(Takhzyro),
caplacizumab
(Cablivi),
mogamulizumab
(Poteligeo),
moxetumomab
pasudodox
(Lumoxiti),
cemiplimab
(Libtayo),
ibalizumab
(Trogarzo),
tildrakizumab
(Ilumetri,
Ilumya),
emapalumab
(Gamifant))
treat
wide
variety
diseases
granted
either
European
Union
(EU)
United
States
(US).
As
November
4
(sacituzumab
govitecan,
ravulizumab,
risankizumab,
romosozumab)
considered
their
marketing
EU
US,
additional
3
developed
by
Chinese
companies
(tislelizumab,
sintilimab,
camrelizumab)
China.
addition,
our
show
product
candidates
(leronlimab,
brolucizumab,
polatuzumab
vedotin)
may
enter
end
least
12
(eptinezumab,
teprotumumab,
crizanlizumab,
satralizumab,
tanezumab,
isatuximab,
spartalizumab,
MOR208,
oportuzumab
monatox,
TSR-042,
enfortumab
vedotin,
ublituximab)
2019.
Finally,
found
approximately
half
(18
33)
cancer
immune
checkpoint
modulators
antibody-drug
conjugates.
Of
these,
7
(tremelimumab,
BCD-100,
omburtamab,
mirvetuximab
soravtansine,
trastuzumab
duocarmazine,
depatuxizumab
mafodotin)
evaluated
studies
primary
completion
dates
late
2019,
thus
'antibodies
watch'.
We
look
forward
documenting
progress
made
these
other
next
installment
series.
New England Journal of Medicine,
Год журнала:
2021,
Номер
386(7), С. 617 - 628
Опубликована: Дек. 12, 2021
Sickle
cell
disease
is
characterized
by
the
painful
recurrence
of
vaso-occlusive
events.
Gene
therapy
with
use
LentiGlobin
for
sickle
(bb1111;
lovotibeglogene
autotemcel)
consists
autologous
transplantation
hematopoietic
stem
and
progenitor
cells
transduced
BB305
lentiviral
vector
encoding
a
modified
β-globin
gene,
which
produces
an
antisickling
hemoglobin,
HbAT87Q.
Sickle
cell
disease
(SCD)
is
an
inherited
disorder
of
hemoglobin,
characterized
by
formation
long
chains
hemoglobin
when
deoxygenated
within
capillary
beds,
resulting
in
sickle-shaped
red
blood
cells,
progressive
multiorgan
damage,
and
increased
mortality.
An
estimated
300
000
infants
are
born
annually
worldwide
with
SCD.
Most
individuals
SCD
live
sub-Saharan
Africa,
India,
the
Mediterranean,
Middle
East;
approximately
100
US.
Observations
diagnosed
through
newborn
screening
programs,
where
available,
or
patients
present
unexplained
severe
atraumatic
pain
normocytic
anemia.
In
SCD,
sickling
hemolysis
cells
result
vaso-occlusion
associated
ischemia.
repeated
episodes
acute
chest
syndrome,
other
complications
including
stroke,
chronic
pain,
nephropathy,
retinopathy,
avascular
necrosis,
priapism,
leg
ulcers.
US,
nearly
all
children
survive
to
adulthood,
but
average
life
expectancy
remains
20
years
less
than
general
population,
higher
mortality
as
transition
from
pediatric
adult-focused
health
care
systems.
Until
2017,
hydroxyurea,
which
increases
fetal
reduces
sickling,
was
only
disease-modifying
therapy
available
for
first-line
most
Three
additional
therapies,
L-glutamine,
crizanlizumab,
voxelotor,
have
been
approved
adjunctive
second-line
agents.
clinical
trials,
L-glutamine
reduced
hospitalization
rates
33%
mean
length
stay
11
7
days
compared
placebo.
Crizanlizumab
crises
2.98
1.63
per
year
Voxelotor
at
least
1
g/dL,
significantly
more
placebo
(51%
vs
7%).
Hematopoietic
stem
transplant
curative
therapy,
it
limited
donor
availability,
best
results
seen
a
matched
sibling
donor.
While
not
likely
develop
addiction
medications
population.
Conclusions
Relevance
people
hemolytic
anemia,
syndrome;
incidence
retinopathy;
span
that
shorter
hydroxyurea
voxelotor
US
since
2017
treatments,
hematopoietic
now
standard
disease.
Cell,
Год журнала:
2024,
Номер
187(5), С. 1076 - 1100
Опубликована: Фев. 1, 2024
Genome
editing
has
been
a
transformative
force
in
the
life
sciences
and
human
medicine,
offering
unprecedented
opportunities
to
dissect
complex
biological
processes
treat
underlying
causes
of
many
genetic
diseases.
CRISPR-based
technologies,
with
their
remarkable
efficiency
easy
programmability,
stand
at
forefront
this
revolution.
In
Review,
we
discuss
current
state
CRISPR
gene
technologies
both
research
therapy,
highlighting
limitations
that
constrain
them
technological
innovations
have
developed
recent
years
address
them.
Additionally,
examine
summarize
landscape
applications
context
health
therapeutics.
Finally,
outline
potential
future
developments
could
shape
coming
years.
New England Journal of Medicine,
Год журнала:
2021,
Номер
386(2), С. 138 - 147
Опубликована: Дек. 12, 2021
Gene
therapy
with
LentiGlobin
for
sickle
cell
disease
(bb1111,
lovotibeglogene
autotemcel)
consists
of
autologous
transplantation
a
patient's
hematopoietic
stem
cells
transduced
the
BB305
lentiviral
vector
that
encodes
βA-T87Q-globin
gene.
Acute
myeloid
leukemia
developed
in
woman
approximately
5.5
years
after
she
had
received
as
part
initial
cohort
(Group
A)
HGB-206
study.
An
analysis
peripheral-blood
samples
revealed
blast
contained
insertion
site.
The
results
an
investigation
causality
indicated
was
unlikely
to
be
related
insertion,
given
location
site,
very
low
transgene
expression
cells,
and
lack
effect
on
surrounding
genes.
Several
somatic
mutations
predisposing
acute
were
present
diagnosis,
which
suggests
patients
are
at
increased
risk
hematologic
malignant
conditions
transplantation,
most
likely
because
combination
risks
associated
underlying
disease,
procedure,
inadequate
control
treatment.
(Funded
by
Bluebird
Bio.).
New England Journal of Medicine,
Год журнала:
2024,
Номер
390(18), С. 1649 - 1662
Опубликована: Апрель 24, 2024
Exagamglogene
autotemcel
(exa-cel)
is
a
nonviral
cell
therapy
designed
to
reactivate
fetal
hemoglobin
synthesis
by
means
of
ex
vivo
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)-Cas9
gene
editing
autologous
CD34+
hematopoietic
stem
and
progenitor
cells
(HSPCs)
at
the
erythroid-specific
enhancer
region
Blood,
Год журнала:
2022,
Номер
140(17), С. 1837 - 1844
Опубликована: Июнь 3, 2022
During
hemolysis,
erythrophagocytes
dispose
damaged
red
blood
cells.
This
prevents
the
extracellular
release
of
hemoglobin,
detoxifies
heme,
and
recycles
iron
in
a
linked
metabolic
pathway.
Complementary
to
this
process,
haptoglobin
hemopexin
scavenge
shuttle
cell
toxins
hemoglobin
heme
cellular
clearance.
Pathological
hemolysis
outpaces
macrophage
capacity
scavenger
synthesis
across
diversity
diseases.
imbalance
leads
hemoglobin-driven
disease
progression.
To
meet
void
treatment
options,
protein-based
therapeutics
are
clinical
development.
