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The ESSENCE of exon inclusion

Designing synthetic proteins that can repair aberrant splicing mutations.

Jonathan Weitzman(jonathanweitzman@hotmail.com)

Many human genetic diseases are due to point mutations that cause aberrant splicing. These may affect splice site sequences directly, or may disrupt regulatory elements such as exonic splicing enhancers (ESE). ESEs are binding sites for serine/arginine-rich (SR) splicing factor proteins. In an Advanced Online Publication in Nature Structural Biology, Luca Cartegni and Adrian Krainer, at Cold Spring Harbor Laboratory, New York, US, describe the design of synthetic proteins that can promote specific exon inclusion (Nature Structural Biology, DOI:10.1038/nsb887, 13 January 2003).

Cartegni and Krainer fused the minimal RS domain from SR proteins with an antisense moiety for targeting to specific exons. They demonstrated the efficiency of this technique using transcripts from the BRCA1 and SMN2 genes. This approach (which they dubbed ESSENCE — exon-specific splicing enhancement by small chimeric effectors) may be used to designed therapeutic compounds...

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