Pharmacokinetic Considerations in the Use of Genes as Pharmaceuticals

  • Fred D. Ledley


Two paradigms for the clinical application of direct, somatic gene therapy can be distinguished. In one paradigm, genes are administered at a single point in time with the expectation that these genes will associate permanently with the target cell, producing therapeutic amounts of the gene product indefinitely. This requires the use of vectors which integrate their genetic material into the chromosomes of the host cell or persist in an episomal state through episomal replication or a latent phase. In the other paradigm, genes are administered like conventional pharmaceuticals with the knowledge that the gene will be eliminated from the cell after a finite and predictable period of time during which the therapeutic gene product is expressed. This can be achieved with the use of DNA-vectors which produce transient expression, or with the use of viral vectors which provide short-term expression but are incapable of persisting indefinitely in the target cell. This paradigm envisions the use of genes in a manner analogous to conventional medicines to treat acute diseases or to establish steady-state levels of the therapeutic product.


Order Kinetic Vector Sequence Mediate Gene Transfer Methylmalonic Acidemia Somatic Gene Therapy 
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© Birkhäuser Boston 1994

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  • Fred D. Ledley

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