Annemieke Aartsma-Rus: Design of Exon Skipping Oligonucleotides

Antisense-mediated splicing modulation utilizes antisense oligonucleotides (ASOs) to manipulate the splicing by sterically blocking the binding of splicing factors to pre-mRNA transcripts. While in industry often oligo walks are used to identify the most optimal ASO, generally academic groups do not have the funds to do this and can design only a limited number of ASOs for testing. While ASO design for splicing modulation is partially a trial and error approach, some lessons can be learnt from previous efforts.