Alternative Splicing

Synonyms

mRNA splice variants

Definition

Antisense technology has also been used to manipulate alternative splicing patterns altering the ratio of different splice variants of a gene and its function. Several diseases are linked to mutated alternative splicing of specific genes such as thalassemia, Duchenne muscular dystrophy, cystic fibrosis, and parkinsonism linked to chromosome 17. The therapeutic potential of this antisense approach, for example, to silence gene mutations responsible for defect pre-mRNA splicing is enormous.

Antisense oligonucleotidesthat alter splicing should be different from those designed to downregulate gene expression and should be chemically modified such as to prevent activation of RNase H as this would destroy pre-mRNA before splicing, to have a higher nuclease resistance and affinity for the target sequence. According to ex vivo intracellular localization studies, the antisense oligonucleotides need to enter the nucleus for successful modulation of...