Alternative RNA Splicing Therapy for Spinal Muscular Atrophy
Dr. Phil Sharp and Dr. Charlotte Sumner describe how RNA splicing can be used as a therapy for SMA.
Phil Sharp: I think what is surprising and is a frontier that I find very promising is we now understand how diseases are related to alternative splicing and to mutations that affect alternative splicing. We understand that we can make small unusual structured drugs called oligonucleotides, which is the same material DNA is made out of by and large, and introduce that into cells and shift the splicing process. And if we can shift splicing process then we should be able to control some of the changes due to mutations in disease processes.
Charlotte Sumner: So one very elegant way to treat SMA is to try and alter that process of alternative splicing of exon 7 of these RNAs that arise from SMN2. And in fact in that way, you would convert all of that truncated form of the RNA that's useless and it makes a useless protein. If you could convert all of that to full length transcript and make all of that full length transcript make normal SMN protein, you could imagine that would be a very powerful way to basically restore the SMN2 gene to the function of what an SMN1 gene would do. And so that's been another major push in the field to try and identify ways to alter this balance of including exon 7.