There's a family of mice known as
Beethoven.
They carry an inherited
genetic mutation that causes a
progressive hearing loss.
They were named after Ludwig van
Beethoven, who also suffered
from a progressive hearing loss.
Now we don't know the real cause of
Beethoven's hearing loss but we do know
that there's an identical genetic
mutation in humans that causes a
progressive hearing loss.
To try to prevent deafness in the
Beethoven mouse,
we reasoned that the mouse had one
normal copy of the gene that would be
adequate, and all we needed to do was to
disrupt the mutant copy of the gene.
We used a molecule known as a guide RNA
together with a CRISPR Cas9 enzyme
that would recognize that disease gene,
cut it, and then leave the correct,
healthy gene intact.
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The system uses two layers of
recognition.
One is the guide RNA, one is
the Cas9 enzyme itself, binding to
the mutant copy of the DNA
In order to recognize it.
Further analysis at the DNA level revealed that our gene editing approach was very specific.
Up to 99% of the Beethoven DNA was edited,
but not the correct healthy DNA.
So we injected this new Cas9 system
into the inner ears of newborn mice
and the mice developed normally
and their hearing was preserved.
In fact, in some of the treated animals,
their hearing levels were
indistinguishable from normal mice.
We had human cells in a dish that had
the same mutation and we were able to
correct that mutation, giving us hope
that eventually we can carry this
therapy into human families as well.
We realized that the system could be
applied to many other dominantly
inherited diseases.
We believe that our approach could
be used to target over
20% of inherited diseases caused by
mutations in a single gene copy.
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