Nature Biotechnology,
Journal Year:
2023,
Volume and Issue:
41(10), P. 1446 - 1456
Published: Feb. 16, 2023
Most
short
sequences
can
be
precisely
written
into
a
selected
genomic
target
using
prime
editing;
however,
it
remains
unclear
what
factors
govern
insertion.
We
design
library
of
3,604
various
lengths
and
measure
the
frequency
their
insertion
four
sites
in
three
human
cell
lines,
different
editor
systems
varying
DNA
repair
contexts.
find
that
length,
nucleotide
composition
secondary
structure
sequence
all
affect
rates.
also
discover
3'
flap
nucleases
TREX1
TREX2
suppress
longer
sequences.
Combining
features
machine
learning
model,
we
predict
relative
insertions
site
with
R
=
0.70.
Finally,
demonstrate
how
our
accurate
prediction
user-friendly
software
help
choose
codon
variants
common
fusion
tags
insert
at
high
efficiency,
provide
catalog
empirically
determined
rates
for
over
hundred
useful
Science,
Journal Year:
2023,
Volume and Issue:
379(6629)
Published: Jan. 19, 2023
The
advent
of
clustered
regularly
interspaced
short
palindromic
repeat
(CRISPR)
genome
editing,
coupled
with
advances
in
computing
and
imaging
capabilities,
has
initiated
a
new
era
which
genetic
diseases
individual
disease
susceptibilities
are
both
predictable
actionable.
Likewise,
genes
responsible
for
plant
traits
can
be
identified
altered
quickly,
transforming
the
pace
agricultural
research
breeding.
In
this
Review,
we
discuss
current
state
CRISPR-mediated
manipulation
human
cells,
animals,
plants
along
relevant
successes
challenges
present
roadmap
future
technology.
Nature Biotechnology,
Journal Year:
2021,
Volume and Issue:
39(8), P. 949 - 957
Published: May 19, 2021
Abstract
Most
known
pathogenic
point
mutations
in
humans
are
C•G
to
T•A
substitutions,
which
can
be
directly
repaired
by
adenine
base
editors
(ABEs).
In
this
study,
we
investigated
the
efficacy
and
safety
of
ABEs
livers
mice
cynomolgus
macaques
for
reduction
blood
low-density
lipoprotein
(LDL)
levels.
Lipid
nanoparticle–based
delivery
mRNA
encoding
an
ABE
a
single-guide
RNA
targeting
PCSK9
,
negative
regulator
LDL,
induced
up
67%
editing
(on
average,
61%)
34%
26%)
macaques.
Plasma
LDL
levels
were
stably
reduced
95%
58%
32%
14%
macaques,
respectively.
was
cleared
rapidly,
no
off-target
genomic
DNA
found.
Re-dosing
did
not
increase
editing,
possibly
owing
detected
humoral
immune
response
upon
treatment.
These
findings
support
further
investigation
treat
patients
with
monogenic
liver
diseases.
