Gene therapy of T helper cells in HIV infection: Mathematical model of the criteria for clinical effect

Autor: Susanne Dam Nielsen, Ole Søgaard Lund, J. O. Nielsen, Ole Lund, Kristian Schønning, Gregers J. Gram, Erik Mosekilde, John-Erik Stig Hansen
Rok vydání: 1997
Předmět:
Zdroj: Bulletin of Mathematical Biology. 59:725-745
ISSN: 1522-9602
0092-8240
DOI: 10.1007/bf02458427
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: