CORRECTION OF THE GROWTH DEFECT IN DWARF MICE WITH NONAUTOLOGOUS MICROENCAPSULATED MYOBLASTS - AN ALTERNATE APPROACH TO SOMATIC GENE-THERAPY

Most of the currently approved human gene therapy protocols depend on genetic modification of autologous cells. We propose an alternate and potentially more cost-effective approach by implanting genetically mod ified ''universal'' cell lines to deliver desired gene products to non autologous recipients. The recombinant allogeneic cells are protected from rejection after implantation by enclosure within immune-protectiv e alginate-poly-L-lysine-alginate microcapsules. The clinical efficacy of this strategy is now demonstrated by implanting microencapsulated allogeneic myoblasts engineered to secrete mouse growth hormone into t he growth hormone-deficient Snell dwarf mice. The treated mutants atta ined increases in linear growth, body weights, peripheral organ weight s, and tibial growth plate thickness significantly greater than those of the untreated controls. Secondary response to the exogenous growth hormone stimulation also resulted in increased fatty acid metabolism d uring the first month post-implantation. The microcapsules retrieved a fter about 6 months of implantation appeared intact. The encapsulated myoblasts retained a viability of >60% and continued to secrete mouse growth hormone. Thus, implantation of nonautologous recombinant cells corrected partially the pleiomorphic effects of a transcription factor mutation in the Snell dwarf mice and the encapsulated cells remained functional for at least 6 months. This simple method of delivery recom binant gene products in vivo is a benign procedure, obviates the need for patient-specific genetic modification, and is amenable to industri al-scale quality control. It should have wide applications in therapie s requiring a systemic continuous supply of recombinant gene products.