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Towards Stronger Microcapsules for Non-Autologous Somatic Gene Therapy

Van Raamsdonk, J. (Department of Medical Sciences, McMaster University, Canada)
Chang, P. (Department of Pediatrics, McMaster University, Canada)

Contact Person: Jeremy M. Van Raamsdonk (vanraaj@mcmaster.ca)


In our laboratory, microencapsulation is used in a novel approach to gene therapy called somatic gene therapeutics. Somatic gene therapeutics involves encapsulating recombinant cell lines, created to secrete a therapeutic protein, in alginate-polylysine-alginate(APA) microcapsules. The microcapsules serve to immuno-isolate cell lines for implantation thereby enabling the implantation of the same non-autologous cell line into different recipients and providing a potentially cost-effective method for gene therapy. However, the success of this technique is critically dependent on the structural stability of the microcapsules. Although our strategy has been effective at delivering therapeutic proteins using murine models, trials in canine models have not seen prolonged delivery. The limited success of our approach in canine models has been attributed to poor survival of the APA microcapsules in vivo. Consequently, we have developed several tests to measure the structural stability of the microcapsules. These tests can be used over time to individually test the factors that may weaken microcapsules in vivo or they can be used simply to compare the strength of different types of microcapsules. Our primary tests include an osmotic pressure test and a cone and plate shearing test. Both the osmotic pressure test and the shearing test have been used to confirm that solid APA microcapsules are stronger than hollow APA microcapsules and that barium cross-linked microcapsules are stronger than calcium cross-linked microcapsules. While these two examples had predictable results, they served to confirm the validity of our structural stability tests. The microcapsule strength tests have also been used to compare several new types of microcapsules and some of these new microcapsules have been shown to be significantly stronger than the common APA microcapsules.

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Poster Number PAvan raamsdonk0239
Keywords: encapsulation, immunoisolation, gene therapy, xenotransplant, biomaterials

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Van Raamsdonk, J.; Chang, P.; (1998). Towards Stronger Microcapsules for Non-Autologous Somatic Gene Therapy. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/pharmtox/van_raamsdonk0239/index.html
© 1998 Author(s) Hold Copyright