Potential therapeutic strategies targeting splicing factor mutations and splicing changes. A schematic of the major spliceosome components illustrates potential strategies to modulate splicing. (A) Small molecules (eg, PB and FR derivatives and analogs) alter the function of the U2 snRNP, leading to the accumulation of unspliced products. (B) Inhibition of SR protein phosphorylation alters intracellular trafficking and binding of SR proteins to exonic splice enhancers, leading to altered utilization of cassette exons. (C) Oligonucleotides and transplicing modulators can change splicing preference at specific targets. (D) Depletion or replacement of spliced products. BPS, branch point sequence; CLK, CDC-like kinase; PPT, polypyrimidine tract; SRPK, SR protein kinase.