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Most gene therapy approaches to treat HIV/AIDS aim to down regulate expression of the cell surface HIV co-receptor CCR5. However this approach appears unlikely to work due to the difficulty in modifying patient cells. A much better strategy is to up regulate HIV cell surface receptors on cells natively or rendered non permissive to HIV replication. This approach significantly decrease T cell loss during the primary phase of the infection and requires the modification of far fewer cells. Alternately, liver cells can be efficiently modified to express CD4 and the CCR5 and CXCR4 co-receptors. These cells are naturally non permissive to HIV replication. This strategy is also applicable to other viruses.