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 -