Manipulating Splicing May Treat Genetic Diseases

Scientists have developed a new technique to correct genetic mutations that result in abnormal splicing, the cause of spinal muscular atrophy.

Splicing is part of the process by which genes are converted into proteins. To make proteins, genes first need to be processed into RNA. The information in the genes is broken up into islands of information called exons, which need to be stitched together, while the meaningless sequences are removed. If the sequence of an exon is changed, splicing can be disrupted, causing genetic mutations.

In the study, researchers were able to stick the right sequences back into the exon by using short pieces of RNA (oligos), which stick to the exon of interest and had been modified to recruit signals that influence splicing. In this way, the splicing reaction can be manipulated. The treatment was tested on cells from a patient suffering from spinal muscular atrophy. By putting these oligos into the cells, much of the protein required for the splicing process could be produced, allowing normal development of the cells.

"Although oligos have previously been developed to block expression of genes, this research indicates that we can also use them to restore the proper expression of defective genes,” said Ian Eperon, professor at the University of Leicester (UK; www.le.ac.uk), who conducted the study with colleagues at Imperial College London and Hammersmith Hospital (London, UK).




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