Waddington, Simon N and Buckley, Suzanne M K and Nivsarkar, Megha and Jezzard, Sarah and Schneider, Holm and Dahse, Thomas and Kemball-Cook, Geoff and Miah, Maznu and Tucker, Nick and Dallman, Margaret J and Themis, Mike and Coutelle, Charles (2003) In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor. Blood, 101 (4). pp. 1359-1366. ISSN 0006-4971Full text not available in this repository. (Request a copy from the Strathclyde author)
The fundamental hypotheses behind fetal gene therapy are that it may be possible (1) to achieve immune tolerance of transgene product and, perhaps, vector; (2) to target cells and tissues that are inaccessible in adult life; (3) to transduce a high percentage of rapidly proliferating cells, and in particular stem cells, with relatively low absolute virus doses leading to clonal transgene amplification by integrating vectors; and (4) to prevent early disease manifestation of genetic diseases. This study provides evidence vindicating the first hypothesis; namely, that intravascular prenatal administration of an adenoviral vector carrying the human factor IX (hFIX) transgene can induce immune tolerance of the transgenic protein. Following repeated hFIX protein injection into adult mice, after prenatal vector injection, we found persistence of blood hFIX and absence of hFIX antibodies in 5 of 9 mice. Furthermore, there was substantial hFIX expression after each of 2 reinjections of vector without detection of hFIX antibodies. In contrast, all adult mice that had not been treated prenatally showed a rapid loss of the injected hFIX and the development of high hFIX antibody levels, both clear manifestations of a strong immune reaction.
|Keywords:||adenoviridae, animals, antibodies, factor IX, female, fetus, gene expression, genetic vectors, humans, immune tolerance, kinetics, liver, mice, myocardium, pregnancy, recombinant proteins, time factors, transfection, Pharmacy and materia medica, Biochemistry, Cell Biology, Immunology, Hematology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||13 Jul 2011 08:56|
|Last modified:||02 Sep 2016 02:40|