Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect.
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Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect. / Lund, O; Lund, O S; Gram, G; Nielsen, S D; Schønning, Kristian; Nielsen, Jens Ole; Hansen, J E; Mosekilde, E.
I: Bulletin of Mathematical Biology, Bind 59, Nr. 4, 1997, s. 725-745.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
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TY - JOUR
T1 - Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect.
AU - Lund, O
AU - Lund, O S
AU - Gram, G
AU - Nielsen, S D
AU - Schønning, Kristian
AU - Nielsen, Jens Ole
AU - Hansen, J E
AU - Mosekilde, E
PY - 1997
Y1 - 1997
N2 - This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.
AB - This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.
M3 - Journal article
VL - 59
SP - 725
EP - 745
JO - Bulletin of Mathematical Biology
JF - Bulletin of Mathematical Biology
SN - 0092-8240
IS - 4
ER -
ID: 34064769