By blocking the exon 5 splice site, exon 4 is now used more. However, targeting the 3' splice site to induce exon skipping rarely is efficient - probably because U2AF and U2snRNP bind with relatively high efficiency and force off the ASO. However, this takes time and then exon 4 gets to be included.

U2snRNP inhibotors are novel types of drugs. 3 groups based on the target protein in the complex.
U2snRNP is connected to genetic instability. Can the drugs induce lethal genomic instability and synergize w classical dna,damage drugs?
Shows data that yes...

⭐ #NARBreakthrough! ⭐
🔬 New study by @magistratolab.bsky.social and @pokorna.bsky.social reveals how TAT-SF1 acts as a “molecular latch,” storing strain in #U2snRNP to drive branch-helix formation. A “loaded-spring” model for #splicingfidelity.
📖 Read the article: doi.org/10.1093/nar/...