Duplikacje do pominięcia przez Exon Skipping

Naukowcy próbują zastosować exon skipping do pominięcia duplikacji. Na razie są to tylko próby przedkliniczne. Nie udowodniono, że istnieją narzędzia pozwalające wykorzystać tę technologię przy duplikacjach. Nie mniej jednak zamieszczam poniżej tabelę, która pokazuje, jaki exon należałoby pominąć  przy konkretnej duplikacji. Gdyby udało się tego dokonać pacjenci z duplikacjami byliby całkowicie uleczeni.


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Exon skipping to repair duplications. Duplications of
one or more exons causing a shift of the reading frame
happened in about 7% of all Duchenne patients.
In principle, they can be repaired by exon skipping also,
if it were possible to remove the one additional set of the
duplicated exons without touching the first, the original set
of exons, the new dystrophin protein would have the normal
size. If enough new and normal dystrophin were produced
to stop the muscle degradation, this treatment would
lead to a cure, and not only to a therapy.
The problem is that the antisense oligos recognize both
sets of exons that are exactly the same. So if one tries to
skip one, both will be skipped. For single-exon duplications,
there might be a way out, because in some cases, one
can skip a third exon before or after the duplicated ones,
and thus restore the reading frame. But for larger duplications,
it becomes very complex and thus very challenging,
and may perhaps not be possible at all.
A new project to correct duplications has been started
by Kevin Flanigan and his team at the Nationwide Children’s
Hospital in Columbus/Ohio.
As a duplication of exon 2 is the most common singleexon
duplication in Duchenne patients, a new laboratory
mouse was developed which has such an exon-2 duplication
in its dystrophin gene and which develops symptoms
of a severe muscle disease. As soon as a sufficient
number of these mice have been raised, in-vivo experiments
will be possible for finding a way to repair this
The researchers have already created cell cultures for
laboratory experiments with cell lines from patients with
different duplications. They are now trying to correct these
duplications with the usual exon-skipping antisense oligos
but also with the AAV U7-snRNA technique.
This project is being financed by the American parent
association Cure Duchenne.

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