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Miscellaneous

TKT’s plans for turning on endogenous genes

Pages 325-328 | Published online: 25 Feb 2005
 

Abstract

These patents describe the design and use of gene targeting constructs to generate cells containing novel transcription units each formed by homologous recombination between an endogenous target gene and the targeting construct. Specifically, the targeting constructs include at least: DNA homologous to the target locus, exogenous regulatory sequences and an exogenous exon with an unpaired splice donor site. The new transcription unit is expressed from the exogenous regulatory sequences and includes most or all of the target gene’s coding sequences which in some instances are fused at their 5′ end to exogenous coding sequences. In this way, cells can be generated in which the expression pattern of an endogenous gene is altered (usually up-regulated). Although both patents lay claim to the general design and use of such targeting constructs, detailed claims are made with specific reference to target genes that code for human thrombopoietin (hTPO), β-interferon (β-IFN) and DNAse I in patent WO9629411 and for human erythropoietin (hEPO), Growth hormone (hGH), granulocyte/macrophage-colony stimulating factor (hGM-CSF) and follicle stimulating hormone β (hFSHβ) in patent US5641670. The latter patent also lists more than 50 potential target genes of commercial importance as well as general categories of potential target genes (e.g., genes for hormones, cytokines, enzymes etc.). The patents also lay claim to the resulting homologously recombinant cells, and to their use for the production and use of the protein product of the targeted gene or for delivery to mammals for therapeutic purposes.

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