Engineering drive–selection balance for localized population suppression with neutral dynamics
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(6)
Published: Feb. 4, 2025
While
the
release
of
sterile
males
has
been
highly
successful
in
suppressing
some
pest
populations,
it
is
impractical
for
many
species
due
to
disappearing
after
a
single
generation,
necessitating
large,
repeated
releases
maintain
sufficient
impact.
Synthetic
gene
drives
promise
more
efficient
approaches
since
they
can
increase
frequency
from
rare,
yet
this
also
allows
them
spread
across
landscape,
which
may
not
always
be
desired.
Between
these
two
extremes
are
selectively
neutral
genetic
constructs
persist
at
released,
offering
potential
suppression
that
remains
localized.
One
way
achieve
would
have
perfect
balance,
all
construct
frequencies,
between
drive
increasing
and
selection
decreasing
it.
Here,
we
describe
closely
approximate
balance
using
toxin–antidote
causes
recessive
lethality
or
sterility,
encodes
genomic
editor
makes
dominant
lethal
edits
genome,
provides
protection
against
action
consequences
editing.
Computer
modeling
shows
design
100-fold
than
males,
1,000-fold
when
released
alongside
booster.
We
designs
CRISPR-based
molecular
construction,
including
options
avoid
recoded
genes
as
antidotes.
Language: Английский
Stronger population suppression by gene drive targetingdoublesexfrom dominant female-sterile resistance alleles
Published: April 20, 2025
Abstract
CRISPR
homing
drives
can
be
used
to
suppress
a
population
by
targeting
female
fertility
genes.
They
convert
wild-type
alleles
drive
in
the
germline
of
heterozygotes
homology-directed
repair
after
DNA
cleavage.
However,
resistance
produced
end-joining
pose
great
threat
drive.
prevent
further
recognition
Cas9,
and
therefore
weaken
suppressive
power,
or
even
stop
suppression
if
they
preserve
function
target
gene.
We
multiplexed
gRNAs
doublesex
Drosophila
avoid
functional
create
that
were
dominant
female-sterile.
This
occurred
because
male
dsx
transcript
was
generated
females
disruption
female-specific
splicing
acceptor
site.
rescued
sterility
providing
an
alternate
As
desired,
recessive
sterile
yielded
high
inheritance
among
progeny
both
heterozygotes.
The
dominant-sterile
enabled
stronger
computational
models,
face
modest
efficiency
fitness
costs.
we
found
homozygotes
also
rescue
splice
Attempts
males
with
expression
arrangements
not
successful,
though
some
had
less
severe
intersex
phenotypes.
Though
this
negatively
impacted
drive,
models
showed
it
still
significantly
improved
power.
Therefore,
design
may
have
wide
applicability
-based
gene
variety
organisms
intermediate
performance.
Language: Английский
Altering traits and fates of wild populations with Mendelian DNA sequence modifying Allele Sails
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 13, 2024
Population-scale
genome
modification
can
alter
the
composition
or
fate
of
wild
populations.
Synthetic
gene
drives
provide
one
set
tools,
but
their
use
is
complicated
by
scientific,
regulatory,
and
social
issues
associated
with
transgene
persistence
flow.
Here
we
propose
an
alternative
approach.
An
Allele
Sail
consists
a
editor
(the
Wind)
that
introduces
DNA
sequence
edits,
inherited
in
Mendelian
fashion.
Meanwhile,
edits
Sail)
experience
arithmetic,
Super-Mendelian
increase
frequency.
We
model
this
system
identify
contexts
which
single,
low
frequency
release
brings
to
very
high
also
conditions
manipulation
sex
determination
bring
about
population
suppression.
In
regulatory
frameworks
distinguish
between
transgenics
(GMO)
edited
non-transgenic
progeny
(non-GMO)
Sails
may
prove
useful
since
spread
GM
component
be
limited.
authors
introduce
as
method
for
spreading
genetic
changes
throughout
population.
Language: Английский