I just got this from google alerts and am confused. I note that the authors are not Steve Wilton's group, but what do the rest of you know about this? It sounds like they are saying that skipping multiple exon's is not feasible.....
Assessment of the feasibility of exon 45-55 multiexon skipping for duchenne muscular dystrophy
The specific skipping of an exon, induced by antisense oligonucleotides (AON) during splicing, has shown tobe a promising therapeutic approach for Duchenne muscular dystrophy (DMD) patients. As different mutations require skipping of different exons, this approach is mutation dependent.
The skipping of an entire stretch of exons (e.g. exons 45 to 55) has recently been suggested as an approach applicable to larger groups of patients.
However, this multiexon skipping approach is technically challenging. The levels of intended multiexon skips are typically low and highly variable, and may be dependent on the order of intron removal.
We hypothesized that the splicing order might favor the induction of multiexon 45-55 skipping.
Methods: We here tested the feasibility of inducing multiexon 45-55 in control and patient muscle cell cultures using various AON cocktails.
Results: In all experiments, the exon 45-55 skip frequencies were minimal and comparable to those observed in untreated cells.
Conclusion: We conclude that current state of the art does not sufficiently support clinical development of multiexon skipping for DMD.
Author: Laura van Vliet, Christa L de Winter, Judith CT van Deutekom, Gert-Jan B van Ommen and Annemieke Aartsma-Rus
Credits/Source: BMC Medical Genetics 2008, 9:105