Osteogenesis imperfecta (OI), commonly known as "brittle bone disease", is a 
dominant autosomal disorder characterized by bone fragility and abnormalities of 
connective tissue. Biochemical and molecular genetic studies have shown that the 
vast majority of affected individuals have mutations in either the COL1A1 or 
COL1A2 genes that encode the chains of type I procollagen. OI is associated with 
a wide spectrum of phenotypes varying from mild to severe and lethal conditions. 
The mild forms are usually caused by mutations which inactivate one allele of 
COL1A1 gene and result in a reduced amount of normal type I collagen, while the 
severe and lethal forms result from dominant negative mutations in COL1A1 or 
COL1A2 which produce structural defects in the collagen molecule. The most 
common mutations are substitutions of glycine residues, which are crucial to 
formation and function of the collagen triple helix, by larger amino acids. 
Although type I collagen is the major structural protein of both bone and skin, 
the mutations in type I collagen genes cause a bone disease. Some reports showed 
that the mutant collagen can be expressed differently in bone and in skin. Since 
most mutations identified in OI are dominant negative, the gene therapy requires 
a fundamentally different approach from that used for genetic-recessive 
disorders. The antisense therapy, by reducing the expression of mutant genes, is 
able to change a structural mutation into a null mutation, and thus convert 
severe forms of the disease into mild OI type I.