title: CD4(+) T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques.
abstract: 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(+) T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4(+) 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(+) T cells. MazF-modified CD4(+) T cells were clearly detected throughout the experimental period of more than 6 months. The CD4(+) T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4(+) 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(+) 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.
authors.affiliation: Center for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Saito
authors.affiliation: Center for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Chono
authors.affiliation: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Ageyama
authors.affiliation: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
authors.affiliation: Center for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Mineno