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 g ene therapy, Unlike recessive disorders, where expression of a wild-ty pe gene is likely to be sufficient to ameliorate disease pathology the rapies for dominant disorders ape likely to require suppression of the disease allele white maintaining expression of its wild-type counterp art. Marfan syndrome, the most common genetic disorder of the connecti ve tissue, is caused by mutant fibrillin 1 protein exerting a dominant -negative effect. Antisense hammerhead ribozymes - small catalytic RNA s capable of targeting and cleaving specific RNA molecules - appear to offer promise in the development of a therapy for Marfan syndrome.