在存在和不存在长末端重复序列（LTR）特异性引导RNA的情况下，突变型Cas9转录激活因子均可在U1细胞中激活HIV-1。
Mutant Cas9-transcriptional activator activates HIV-1 in U1 cells in the presence and absence of LTR-specific guide RNAs.
作者信息
Kim Veronica, Mears Brian M, Powell Bonita H, Witwer Kenneth W
机构信息
Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine.
出版信息
Matters (Zur). 2017;2017. doi: 10.19185/matters.201611000027. Epub 2017 Jan 12.
Abstract
CRISPR/Cas9 systems have been advanced as promising tools in the HIV eradication armamentarium for sequence-specific disruption or latency reversal. Enthusiasm is balanced by concerns about off-target host genome modification and effects on HIV evolution. In the chronically HIV-1-infected U1 promonocytic latency model, we have confirmed stimulation of HIV-1 production by a mutant Cas9-transcriptional activator and guide RNAs with two guide RNAs apparently more potent than one. However, significant increases were also observed in the absence of guide RNAs. We encourage continued careful evaluation of non-sequence-specific and off-target effects of Cas9-mediated approaches.
摘要
CRISPR/Cas9系统已成为艾滋病根除武器库中用于序列特异性破坏或潜伏逆转的有前景的工具。对脱靶宿主基因组修饰及对HIV进化影响的担忧，平衡了人们的热情。在慢性HIV-1感染的U1单核细胞潜伏模型中，我们已证实一种突变型Cas9转录激活因子和引导RNA可刺激HIV-1产生，其中两个引导RNA的效果明显强于一个。然而，在没有引导RNA的情况下也观察到了显著增加。我们鼓励继续仔细评估Cas9介导方法的非序列特异性和脱靶效应。
相似文献
1
Mutant Cas9-transcriptional activator activates HIV-1 in U1 cells in the presence and absence of LTR-specific guide RNAs.在存在和不存在长末端重复序列（LTR）特异性引导RNA的情况下，突变型Cas9转录激活因子均可在U1细胞中激活HIV-1。
Matters (Zur). 2017;2017. doi: 10.19185/matters.201611000027. Epub 2017 Jan 12.
2
Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism.白细胞介素-6和糖皮质激素通过一种不依赖长末端重复序列的转录后机制，协同诱导慢性感染的U1细胞中1型人类免疫缺陷病毒的表达。
Mol Med. 2001 Oct;7(10):668-78.
3
Targeted mutagenesis of aryl hydrocarbon receptor 2a and 2b genes in Atlantic killifish (Fundulus heteroclitus).大西洋鳉鱼（Fundulus heteroclitus）中芳烃受体2a和2b基因的靶向诱变
Aquat Toxicol. 2015 Jan;158:192-201. doi: 10.1016/j.aquatox.2014.11.016. Epub 2014 Nov 26.
4
Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing.通过CRISPR/Cas9基因编辑从人T淋巴细胞中消除HIV-1基因组
Sci Rep. 2016 Mar 4;6:22555. doi: 10.1038/srep22555.
5
CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures.CRISPR/Cas9 系统靶向 HIV-1 的调节基因，抑制感染 T 细胞培养物中的病毒复制。
Sci Rep. 2018 May 17;8(1):7784. doi: 10.1038/s41598-018-26190-1.
6
Negative regulation of HIV-1 transcription by a heterodimeric NF-κB1/p50 and C-terminally truncated STAT5 complex.NF-κB1/p50 异源二聚体和 C 端截短的 STAT5 复合物对 HIV-1 转录的负调控。
J Mol Biol. 2011 Jul 29;410(5):933-43. doi: 10.1016/j.jmb.2011.03.044.
7
The therapeutic application of CRISPR/Cas9 technologies for HIV.CRISPR/Cas9技术在艾滋病治疗中的应用。
Expert Opin Biol Ther. 2015 Jun;15(6):819-30. doi: 10.1517/14712598.2015.1036736. Epub 2015 Apr 12.
8
Pertussis toxin B-oligomer suppresses IL-6 induced HIV-1 and chemokine expression in chronically infected U1 cells via inhibition of activator protein 1.百日咳毒素B寡聚体通过抑制激活蛋白1来抑制白细胞介素-6诱导的慢性感染U1细胞中HIV-1和趋化因子的表达。
J Immunol. 2006 Jan 15;176(2):999-1006. doi: 10.4049/jimmunol.176.2.999.
9
The cAMP-dependent protein kinase A and protein kinase C-beta pathways synergistically interact to activate HIV-1 transcription in latently infected cells of monocyte/macrophage lineage.环磷酸腺苷（cAMP）依赖性蛋白激酶A和蛋白激酶C-β信号通路协同作用，激活单核细胞/巨噬细胞系潜伏感染细胞中的HIV-1转录。
Virology. 1998 Jun 5;245(2):257-69. doi: 10.1006/viro.1998.9158.
10
Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4 T cells from HIV-1 infection.利用CRISPR-Cas9对HIV共受体CCR5和CXCR4进行基因组编辑可保护CD4 T细胞免受HIV-1感染。
Cell Biosci. 2017 Sep 9;7:47. doi: 10.1186/s13578-017-0174-2. eCollection 2017.
引用本文的文献
1
Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.HIV-1免疫逃逸机制：病毒-宿主蛋白相互作用的作用
Curr Issues Mol Biol. 2025 May 16;47(5):367. doi: 10.3390/cimb47050367.
2
HIV cure strategies: which ones are appropriate for Africa?HIV 治愈策略：哪些策略适合非洲？
Cell Mol Life Sci. 2022 Jul 6;79(8):400. doi: 10.1007/s00018-022-04421-z.
3
Updates on CRISPR-based gene editing in HIV-1/AIDS therapy.基于CRISPR的基因编辑在HIV-1/艾滋病治疗中的进展
Virol Sin. 2022 Feb;37(1):1-10. doi: 10.1016/j.virs.2022.01.017. Epub 2022 Jan 19.
4
Reduce and Control: A Combinatorial Strategy for Achieving Sustained HIV Remissions in the Absence of Antiretroviral Therapy.减少与控制：在不使用抗逆转录病毒疗法的情况下实现持续 HIV 缓解的组合策略。
Viruses. 2020 Feb 8;12(2):188. doi: 10.3390/v12020188.
5
Novel gRNA design pipeline to develop broad-spectrum CRISPR/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients.新型 gRNA 设计流程，用于开发广谱 CRISPR/Cas9 gRNA，以安全靶向患者 HIV-1 准种。
Sci Rep. 2019 Nov 19;9(1):17088. doi: 10.1038/s41598-019-52353-9.
6
Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy.基于 CRISPR/Cas9 的基因编辑在 HIV-1/AIDS 治疗中的应用。
Front Cell Infect Microbiol. 2019 Mar 22;9:69. doi: 10.3389/fcimb.2019.00069. eCollection 2019.
7
Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling.通过长非编码 RNA 和 mRNA 谱分析 dCas9-SAM 介导的 HIV 再激活的全面脱靶分析。
BMC Med Genomics. 2018 Sep 10;11(1):78. doi: 10.1186/s12920-018-0394-2.
8
Broad-Spectrum and Personalized Guide RNAs for CRISPR/Cas9 HIV-1 Therapeutics.用于CRISPR/Cas9 HIV-1治疗的广谱和个性化引导RNA
AIDS Res Hum Retroviruses. 2018 Nov;34(11):950-960. doi: 10.1089/AID.2017.0274. Epub 2018 Aug 27.
9
Designing broad-spectrum anti-HIV-1 gRNAs to target patient-derived variants.设计广谱抗 HIV-1 gRNAs 以靶向患者来源的变异体。
Sci Rep. 2017 Oct 31;7(1):14413. doi: 10.1038/s41598-017-12612-z.
本文引用的文献
1
Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.使用CRISPR/Cas9衍生转录激活系统实现靶向HIV-1潜伏逆转
PLoS One. 2016 Jun 24;11(6):e0158294. doi: 10.1371/journal.pone.0158294. eCollection 2016.
2
Anti-HIV-1 potency of the CRISPR/Cas9 system insufficient to fully inhibit viral replication.CRISPR/Cas9系统的抗HIV-1效力不足以完全抑制病毒复制。
Microbiol Immunol. 2016 Jul;60(7):483-96. doi: 10.1111/1348-0421.12395.
3
CRISPR/Cas9: a double-edged sword when used to combat HIV infection.CRISPR/Cas9：用于对抗HIV感染时的一把双刃剑。
Retrovirology. 2016 May 27;13(1):37. doi: 10.1186/s12977-016-0270-0.
4
Off-target effects of engineered nucleases.工程核酸酶的脱靶效应。
FEBS J. 2016 Sep;283(17):3239-48. doi: 10.1111/febs.13760. Epub 2016 Jun 6.
5
Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study.通过基因编辑切除HIV-1 DNA：一项体内概念验证研究。
Gene Ther. 2016 Aug;23(8-9):690-5. doi: 10.1038/gt.2016.41. Epub 2016 May 19.
6
Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex.使用CRISPR/dCas9激活复合物有效且靶向地激活潜伏的HIV-1 。
Mol Ther. 2016 Mar;24(3):488-98. doi: 10.1038/mt.2015.202. Epub 2015 Nov 19.
7
Off-target Effects in CRISPR/Cas9-mediated Genome Engineering.CRISPR/Cas9介导的基因组工程中的脱靶效应。
Mol Ther Nucleic Acids. 2015 Nov 17;4(11):e264. doi: 10.1038/mtna.2015.37.
8
CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs.CRISPR/导向核糖核酸引导的协同激活介质（SAM）可诱导HIV-1潜伏库的特异性、持续性和强效再激活。
Sci Rep. 2015 Nov 5;5:16277. doi: 10.1038/srep16277.
9
How specific is CRISPR/Cas9 really?CRISPR/Cas9究竟有多特异性？
Curr Opin Chem Biol. 2015 Dec;29:72-8. doi: 10.1016/j.cbpa.2015.10.001. Epub 2015 Oct 24.
10
Highly efficient Cas9-mediated transcriptional programming.高效的Cas9介导的转录编程。
Nat Methods. 2015 Apr;12(4):326-8. doi: 10.1038/nmeth.3312. Epub 2015 Mar 2.
Zotero 插件