Here is an example of an unusual outcome from modifying splicing. Vivo-Morpholinos targeting exon 9 caused skipping of exon 9 and inclusion of exon 10. In normal alternative splicing of this RNA, either exon 9 is included and exon 10 is excised (Pkm1) or exon 9 is excised and exon 10 is excluded (Pkm2).
"Two MOs complementary to the 3′ splice site of exon 9 or one MO complementary to the 5′ splice site of exon 9 were used to block exon 9 inclusion and promote a concurrent inclusion of exon 10 (Fig. 6A and Fig. S3). All three MOs robustly induced skipping of exon 9 and inclusion of exon 10, with MO #2 the most effective (Figs. 6 A–C and Fig. S3). A minor product indicating skipping of both exons 9 and 10 was also observed, as described previously (23, 31)."
Gao Z, Cooper TA. Reexpression of pyruvate kinase M2 in type 1 myofibers correlates with altered glucose metabolism in myotonic dystrophy. PNAS USA. 2013; [Epub ahead of print] doi:10.1073/pnas.1308806110
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