CD4 super(+) T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques

• Published in: Molecular therapy. Nucleic acids 2014-06, Vol.3, p.e168-e168
• Main Authors: Saito, Naoki, Chono, Hideto, Shibata, Hiroaki, Ageyama, Naohide, Yasutomi, Yasuhiro, Mineno, Junichi
• Format: Article
• Language: English
• Subjects: Escherichia coli; Human immunodeficiency virus 1; Lentivirus; Macaca mulatta; Simian/human immunodeficiency virus
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1038/mtna.2014.20

MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine-cytosine-adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4 super(+) T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4 super(+) T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4 super(+) T cells. MazF-modified CD4 super(+) T cells were clearly detected throughout the experimental period of more than 6 months. The CD4 super(+) T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4 super(+) T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4 super(+) T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy.