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Science 8 May 1987:
Vol. 236. no. 4802, pp. 714 - 718
DOI: 10.1126/science.3472348
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Articles

Science, Vol 236, Issue 4802, 714-718
Copyright © 1987 by American Association for the Advancement of Science

articles

Implantation of genetically engineered fibroblasts into mice: implications for gene therapy

RF Selden, MJ Skoskiewicz, KB Howie, PS Russell, and HM Goodman

In a variety of human genetic diseases, replacement of the absent or defective protein provides significant therapeutic benefits. As a model for a somatic cell gene therapy system, cultured murine fibroblasts were transfected with a human growth hormone (hGH) fusion gene and cells from one of the resulting clonal lines were subsequently implanted into various locations in mice. Such implants synthesized and secreted hGH, which was detectable in the serum. The function of the implants depended on their location and size, and on the histocompatibility of the donor cells with their recipients. The expression of hGH could be modified by addition of regulatory effectors, and, with appropriate immunosuppression, the implants survived for more than 3 months. This approach to gene therapy, here termed "transkaryotic implantation," is potentially applicable to many genetic diseases in that the transfected cell line can be extensively characterized prior to implantation, several anatomical sites are suitable for implantation, and regulated expression of the gene of therapeutic interest can be obtained.


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Systemic delivery of human growth hormone by injection of genetically engineered myoblasts.
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High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors.
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