DELIVERY OF RECOMBINANT GENE-PRODUCTS WITH MICROENCAPSULATED CELLS IN-VIVO

If established cultured cell lines genetically modified to secrete des ired gene products could be implanted in different allogeneic recipien ts without immune rejection, novel gene products would be delivered mo re cost effectively. We tested this strategy by encapsulating mouse Lt k- cells transfected with the human growth hormone (hGH) gene in immun oprotective permselective alginate microcapsules. Allogeneic mice impl anted with these microcapsules demonstrated hGH in their circulation ( 0.1-1.5 ng/ml serum) within the first 2 weeks. Control mice implanted with only the transfected cells without microcapsules did not demonstr ate significant levels of circulating hGH. By about 3 weeks, antibodie s against hGH developed in the microcapsule-implanted mice. The immune response was detected only against the hGH and no other secretory pro ducts from the transfected cells. The antibody titer continued to esca late for more than three months, thus demonstrating indirectly the con tinued delivery of the growth hormone. The persistent expression of th e transgene and survival of the transfected cells were verified when t he microcapsules were retrieved periodically to demonstrate that the e ncapsulated cells remained viable, proliferative, and productive of hG H even by 78-111 days. In conclusion, delivering gene products with ge netically modified allogeneic cells in vivo has been shown feasible fo r prolonged periods. This technology should have potential application s in somatic gene therapy and in treatment of other somatic diseases.