Towards an RNA-based therapy for Marfan syndrome.

Dominant genetic disorders, particularly those due to a mutant protein exerting a dominant-negative effect, present a unique challenge for gene therapy. Unlike recessive disorders, where expression of a wild-type gene is likely to be sufficient to ameliorate disease pathology, therapies for dominant disorders are likely to require suppression of the disease allele while maintaining expression of its wild-type counterpart. Marfan syndrome, the most common genetic disorder of the connective tissue, is caused by mutant fibrillin 1 protein exerting a dominant-negative effect. Antisense hammerhead ribozymes--small catalytic RNAs capable of targeting and cleaving specific RNA molecules--appear to offer promise in the development of a therapy for Marfan syndrome.