Targeted Gene Transfer into CD4 Positive Cells by HIV-Based Retroviral Vectors
Because CD4 is the major receptor for HIV infection, HIV based retroviral vectors are capable of targeted and efficient gene transfer into CD4 positive helper T cells. The strict T cell tropism of the HIV vector should be important for the development of gene therapy for AIDS. Another feature is that HIV can infect non-dividing cells. Therefore, the HIV vector may also be useful for gene therapy targeting slow- or non-dividing cells such as hematopoietic stem cells and neural cells. We developed a strategy to use the HIV vector for gene transfer into non-lymphoid cells. A replication defective adenovirus vector containing the human CD4 gene was constructed. Using this recombinant adenovirus vector, the CD4 gene was efficiently transferred and expressed in HeLa, K562, and Raj i cells. These cells were stably transduced with an HIV vector containing the neoR gene. These results indicate that transient expression of CD4 by the adenovirus vector is sufficient to render non-T cells susceptible to gene transfer by the HIV vector. Since adenovirus can infect non-dividing cells, the combination of the adenovirus vector containing the CD4 gene and the HIV vector may be used for stable gene transfer into various types of cells arrested in the cell cycle.
KeywordsAdenovirus Vector Raji Cell Nondividing Cell Recombinant Adenovirus Vector Major Splice Donor
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