What is an exon? Genes are divided into regions called exons and introns. Exons are sections of DNA that code for the protein, and they are interspersed with introns.
Exon-skipping has been showing off its gene therapy promise to scientists looking to treat and cure Duchenne Muscular Dystrophy (DMD), the most severe form of the many different types of muscle wasting diseases. The technology is designed in such a way that it skips over the mutated gene, in fact it completely ignores it.
Duchenne Muscular Dystrophy is caused by a mutation of the dystrophin gene which is present on the X chromosome. It is a very long gene and in individuals with DMD it does not produce the dystrophin protein which is vital for muscle strength and stability.
What happens in exon-skipping gene therapy is that instead of targeting the bad gene and replacing it with a good one, it is neatly sidestepped. The aim is to encourage the cellular machinery to ignore it.
In the DMD research scientists are attempting to change the DMD mutation to the mutation that causes Becker's Muscular Dystrophy. It is a much milder disease and there is some dystrophin production, which does not occur in DMD.
To do this they construct antisense oligonucleotides. These are RNA single-stranded structures of between 20-30 nucleotides in length and are designed specifically to bind to an exon that contains a mutation. The effect of this is that the exon mutation is hidden from the cellular machinery during protein production, and so it is not included in the messenger RNA molecule. The result of this is that a smaller protein is produced, but it is partially functional which reduces the severity of DMD.