Abstract
One theoretical criterion for effective and efficient gene therapy for human genetic disease is stability of a functional gene transferred into defective cells. We are studying the deficiency of hypoxanthine guanine phosphoribosyl transferase (HPRT) in the Lesch Nyhan disease as a model system for the development of methods for gene therapy, and have used retroviral vectors to introduce a functional wild-type human HPRT gene into cultured cells derived from Lesch Nyhan patients. Recipient cells express the foreign gene to a variable extent and demonstrate partial phenotypic reversion of several parameters of aberrant purine biosynthesis characteristic of enzyme-deficient cells. Cells grown without selection and revertants to the HPRT-negative phenotype show the continued presence, loss or rearrangement of the foreign gene and of sequences derived from the vector. The introduction of the HPRT gene into random cellular sites by means of some retroviral vectors therefore clearly leads to variability not only in the degree of gene expression but also in its stability, and we conclude that in the presence or absence of selection pressure, the expression and stability of the newly introduced gene depend on the site of integration into the host cell genome.
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Jolly, D., Willis, R. & Friedmann, T. 834 STABILITY OF GENE TRANSFER IN LESCH NYHAN CELLS. Pediatr Res 19, 249 (1985). https://doi.org/10.1203/00006450-198504000-00864
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DOI: https://doi.org/10.1203/00006450-198504000-00864