Investigating Synthetic Oligonucleotide Targeting of Mir31 in Duchenne Muscular Dystrophy

In conclusion, it could reasonably be argued that if higher oligo doses are required for miR31-modulation, such doses might well be better reserved for exon skipping in the first place. While miR31-modulation potentially offers a universally-applicable therapeutic for DMD, the levels of oligo ostensibly required (as shown here) would unfortunately seem to render this approach impractical under current oligonucleotide chemistries. A recent study (published after the work described here) further showed that several microRNAs may jointly contribute to suppression of dystrophin translation in BMD, including miR146b and miR374a22. MiR31-modulation alone may thus be insufficient in vivo, necessitating PMO-mediated modulation of two or more additional miRs to relieve the translational block. Given that achieving effective delivery of even a single species of oligonucleotide is challenging, such a requirement would further argue strongly against the feasibility of this approach. Appendix Supplementary figure S1: Oligonucleotide sequences and hybridization scheme. Sequences for skipping oligo (M23D), miR31, ‘sponge’ and ‘protector’ oligos (miR31 analogue oligo is simply miR31 sequence, substituting T for U, as morpholinos do not use uracil) Supplementary figure S2: Exon skipping in cell culture Levels of skipping transcript detected in cells differentiated after nucleofection with M23D and miR31-modulatin...
Source: PLOS Currents Muscular Dystrophy - Category: Neurology Authors: Source Type: research