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This experimental cell and gene therapy combination was developed for the treatment of HIV-1 infection, primarily explored in clinical trials involving identical twins (syngeneic donors). The therapy consists of two distinct populations of ex vivo modified CD4+ T lymphocytes. The first population is transduced to express **Rev M10**, a trans-dominant negative mutant of the HIV-1 Rev protein. This mutant competes with wild-type Rev for binding to the Rev response element (RRE), effectively blocking the nuclear export of unspliced and singly-spliced viral mRNAs, thereby halting viral replication. The second population is modified with an **anti-sense trans-activation response (TAR) element**. This antisense RNA sequence is designed to bind to the viral TAR sequence, preventing the HIV-1 Tat protein from initiating efficient transcription of the viral genome. By infusing these 'protected' cells back into the patient, researchers aimed to establish a reservoir of T-cells resistant to the cytopathic effects of HIV-1, potentially maintaining immune function even in the presence of circulating virus.
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