Applications of antisense oligonucleotides in designing a therapy for spinal muscular atrophy

Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease for which there is currently no cure. SMA is caused by an insufficiency of the survival motor neuron protein that leads to loss of motor neurons, muscle denervation and wastage. The study presented in this thesis focused on designing and evaluating splice-switching antisense oligonucleotides that increase survival motor neuron protein levels as a potential therapy for SMA. Furthermore, this study investigates the mechanisms of action of different applications of antisense oligonucleotides, as well as drawing attention to deleterious off­ target effects of particular antisense oligonucleotide chemistries.