Genome Editing Shows Potential for Shrinking Repeat Expansions

Several diseases, many of them involving neurological symptoms, have been linked to expansions of trinucleotide repeat sequences. These repeat expansion disorders include Fragile X syndrome, Huntington’s disease, and various forms of epilepsy and ataxia. In Fragile X, for example, a CGG pattern in the FMR1 gene is associated with the disease: people with 45 CGG copies or fewer are unaffected, while people with more than 200 copies have the syndrome.

This was the foundation for a fascinating project by researchers in France who used a transcription activator-like effector nuclease (TALEN) to target a CAG/CTG repeat in yeast cells, introducing a double-strand break at that location. By doing so, the repeat was deleted; multiple rounds of the TALEN genome editing activity led to repeat tracts with far fewer copies of the trinucleotides. Had these been human cells, the reduction in repeat size would have been enough to shorten a pathogenic region into a harmless region.

Highly Specific Contractions of a Single CAG/CTG Trinucleotide Repeat by TALEN in Yeast,” published in PLoS One (Guy-Franck Richard et al.), details the promising results of using a TALEN for this type of work. It offers the first evidence that a TALEN can shrink a repeat expansion region, which could prove quite promising for biomedical researchers aiming to help people with repeat expansion disorders.

We were glad to see that the scientists used Pippin Prep for their size selection prior to sequencing on the Illumina platform. It’s an honor to be part of such a great effort!

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