title: Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells.
abstract: A major reason that Acquired Immune Deficiency Syndrome (AIDS) cannot be completely cured is the human immunodeficiency virus 1 (HIV-1) provirus integrated into the human genome. Though existing therapies can inhibit replication of HIV-1, they cannot eradicate it. A molecular therapy gains popularity due to its specifically targeting to HIV-1 infected cells and effectively removing the HIV-1, regardless of viral genes being active or dormant. Now, we propose a new method which can excellently delete the HIV provirus from the infected human T cell genome. First, we designed zinc-finger nucleases (ZFNs) that target a sequence within the long terminal repeat (LTR) U3 region that is highly conserved in whole clade. Then, we screened out one pair of ZFN and named it as ZFN-U3. We discovered that ZFN-U3 can exactly target and eliminate the full-length HIV-1 proviral DNA after the infected human cell lines treated with it, and the frequency of its excision was about 30 % without cytotoxicity. These results prove that ZFN-U3 can efficiently excise integrated HIV-1 from the human genome in infected cells. This method to delete full length HIV-1 in human genome can therefore provide a novel approach to cure HIV-infected individuals in the future.
authors: State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Genetics, Fudan University, Shanghai, 200433, China.
authors: Xiying
authors: X
authors: Qu
authors: Pengfei
authors: P
authors: Wang
authors: Donglin
authors: D
authors: Ding
authors: Xiaohui
authors: X
authors: Wang
authors: Gongmin
authors: G
authors: Zhang
authors: Xin
authors: X
authors: Zhou
authors: Lin
authors: L
authors: Liu
authors: Xiaoli
authors: X
authors: Zhu
authors: Hanxian
authors: H
authors: Zeng
authors: Huanzhang
authors: H
authors: Zhu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D049109:Cell Proliferation; D019295:Computational Biology; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D004720:Endonucleases / Q000378:metabolism*; D017353:Gene Deletion; D018390:Gene Targeting; D005814:Genes, Viral; D015894:Genome, Human; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics*; D017422:Sequence Analysis, DNA; D020079:Terminal Repeat Sequences; D014779:Virus Replication; D016335:Zinc Fingers
chemical_list: D004279:DNA, Viral; D004720:Endonucleases