MICROENCAPSULATION OF RECOMBINANT CELLS - A NEW DELIVERY SYSTEM FOR GENE-THERAPY

The therapeutic potential of somatic gene therapy has been extensively investigated in recent years, yet its slow progression into the clini cal setting can be attributed to problems associated with the inabilit y to achieve efficient gene transfers, to obtain sustained level of ex pression of the transfected gene, and the necessity to avoid immunorej ection after transplantation. Here we report on an alternate strategy in gene therapy that overcomes all three problems by immunoisolating g enetically modified cells in a biocompatible membrane, thereby introdu cing a system that can provide sustained delivery of the desired gene product. As a model, mouse fibroblasts transformed with the human grow th hormone gene (Ltk-GH) were encapsulated with an alginate-poly-L-lys ine-alginate membrane. Long-term in vitro studies showed that the enca psulation of the cells was physiologically compatible with growth and survival of the cells. Furthermore, there was a unique pattern of secr etion of the human protein by the encapsulated cells: there was a phas e of steady increase in the secretion of the human growth hormone by e ach cell, followed by a plateau phase. The most convincing evidence of the feasibility of this strategy was provided by the in vivo study: B alb-c mice transplanted with encapsulated Ltk-GH cells had detectable serum levels of human growth hormone (hGH) for the duration of the stu dy (115 days). Moreover, encapsulated cells recovered from a recipient 1 year after the transplantation continued to secrete high levels of hGH in culture.