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Gene Transfer into Primates and Prospects for Gene Therapy in Humans

1989; Academic Press; Linguagem: Inglês

10.1016/s0079-6603(08)60179-8

2211-9108

Kenneth Cornetta, Robert Wieder, W.F. Anderson,

RNA Interference and Gene Delivery

The ability to transfer and express genetic material in mammalian cells presents a new approach to the treatment of many genetic diseases. Retroviral-mediated gene transfer has proven to be an efficient system of gene transfer in vitro. While in vivo expression has been obtained in the mouse, vectors expressing in murine systems do not necessarily express in primates. Retroviral vectors infect primate bone marrow cells and express the transferred genes in vivo. The SAX vector appears to express human adenosine deaminase (ADA) at normal levels, but the infection efficiency is low (<1%) so that the gene product is only detectable in the peripheral blood at low levels. Vector expression disappears after 5 months presumably because of a failure to infect a renewal stem cell. While the level of ADA expression obtained in primates would not appear to be sufficient to correct outright the disease caused by ADA deficiency, it is possible that T-cell progenitors in the marrow will have a selective advantage. T cells expressing an ADA vector would then be able to expand and potentially restore immune function. Unfortunately, this hypothesis will go untested until an animal model for ADA deficiency is found or a human clinical trial is performed.