CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques
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 grow...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116303080 |
| _version_ | 1818525124751523840 |
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| author | Naoki Saito Hideto Chono Hiroaki Shibata Naohide Ageyama Yasuhiro Yasutomi Junichi Mineno |
| author_facet | Naoki Saito Hideto Chono Hiroaki Shibata Naohide Ageyama Yasuhiro Yasutomi Junichi Mineno |
| author_sort | Naoki Saito |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:05:32Z |
| format | Article |
| id | doaj.art-c18825dd4ed74a36b7094fb6d2486507 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-11T06:05:32Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c18825dd4ed74a36b7094fb6d24865072022-12-22T01:18:19ZengElsevierMolecular Therapy: Nucleic Acids2162-25312014-01-013C10.1038/mtna.2014.20CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus MacaquesNaoki Saito0Hideto Chono1Hiroaki Shibata2Naohide Ageyama3Yasuhiro Yasutomi4Junichi Mineno5Center for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, JapanCenter for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, JapanTsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, JapanTsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, JapanTsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, JapanCenter for Cell and Gene Therapy, Takara Bio Inc, Seta, Otsu, Shiga, JapanMazF, 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.http://www.sciencedirect.com/science/article/pii/S2162253116303080gene therapyHIV-1MazFprimate modelrhesus macaqueretroviral vectorSHIV |
| spellingShingle | Naoki Saito Hideto Chono Hiroaki Shibata Naohide Ageyama Yasuhiro Yasutomi Junichi Mineno CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques Molecular Therapy: Nucleic Acids gene therapy HIV-1 MazF primate model rhesus macaque retroviral vector SHIV |
| title | CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques |
| title_full | CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques |
| title_fullStr | CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques |
| title_full_unstemmed | CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques |
| title_short | CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques |
| title_sort | cd4 t cells modified by the endoribonuclease mazf are safe and can persist in shiv infected rhesus macaques |
| topic | gene therapy HIV-1 MazF primate model rhesus macaque retroviral vector SHIV |
| url | http://www.sciencedirect.com/science/article/pii/S2162253116303080 |
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