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Rev transdominant-modified syngeneic CD4+ T lymphocytes + anti-sense trans-activation response element-modified syngeneic CD4+ T lymphocytes

Development stage
Phase 1
Lead developer
National Institute of Allergy and Infectious Diseases
Modality
Cell Therapies, Gene Therapies, RNA Therapeutics → Nucleic Acid Therapeutics
Administration
Intravenous
01

Overview

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.

Other names
Rev M10 + anti-sense TAR modified syngeneic CD4+ T cellsSyngeneic CD4+ T cells modified with RevM10 and antisense TARRev M10 and AS-TAR modified T-lymphocytes
02

Targets

TAR (HIV-1 TAR RNA)Rev (HIV-1 Rev)

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