Splice-switching oligonucleotides demonstrate therapeutic potential in preclinical models and early clinical trials by correcting aberrant splicing or inducing therapeutic splice variants across multiple diseases.
Splice-switching oligonucleotides represent a promising therapeutic approach for diseases caused by aberrant alternative splicing.
Alternative splicing enables a single pre-messenger RNA transcript to yield multiple protein isoforms, making it a major contributor to the diversity of the proteome. While this process is essential for normal development, aberrations in alternative splicing are the cause of a multitude of human diseases. Methods for manipulating alternative splicing would thus be of therapeutic value. Chemically modified antisense oligonucleotides that alter alternative splicing by directing splice site selection have been developed to achieve this end. These splice-switching oligonucleotides (SSOs) have been applied to correct aberrant splicing, induce expression of a therapeutic splice variant, or induce expression of a novel therapeutic splice variant in a number of disease-relevant genes. Recently, in vivo efficacy of SSOs has been reported using animal disease models, as well as in results from the first clinical trial.
Bauman et al. (2009) conducted a review in Genetic and acquired diseases (e.g., Duchenne muscular dystrophy, beta-thalassemia, SMA). Splice-switching oligonucleotides (SSOs) was evaluated. Splice-switching oligonucleotides demonstrate therapeutic potential in preclinical models and early clinical trials by correcting aberrant splicing or inducing therapeutic splice variants across multiple diseases.