GENE THERAPY FOR DRY EYE SYNDROME

摘要

The present invention provides bioconjugates comprising substances which provide increased safety and bioavailability of nucleic acids when used in gene therapy applications. The dihydrazide derivatized hyaluronic acid/nucleic acid compositions of the present invention include hyaluronic acid which has been derivatized with a dihydrazide, preferably adipic dihydrazide, which is crosslinked to a nucleic acid. These compositions may be included in microsphere, film, wafer, matrix, hydrogel, gel and sol formulations. These bioconjugates are useful in gene therapy applications for the treatment of a variety of medical conditions including dry eye syndrome or other medical conditions wherein in increase in the production of hyaluronic acid in the eye would be therapeutic. Further, there may be other medical conditions which could benefit from increased production of hyaluronan, such as osteoarthritis of the articular joints. In the treatment of dry eye syndrome, the compositions of the invention include a hyaluronan synthase gene. When cells in the eye are transfected with and express hyaluronan synthase, hyaluronic acid production is a result. Hyaluronic acid production in the eye provides a therapeutic effect in the treatment of dry eye syndrome by augmenting production of or composition of the ocular tear film. Production of the compositions of the invention is also possible in a process which is easily modified for production of large quantities of dihydrazide derivatized hyaluronic acid.