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HIV crispr cas9

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https://www.readbyqxmd.com/read/27860197/crispr-cas9-the-ultimate-weapon-to-battle-infectious-diseases
#1
REVIEW
M Doerflinger, W Forsyth, G Ebert, M Pellegrini, M J Herold
Infectious diseases are a leading cause of death worldwide. Novel therapeutics are urgently required to treat multi-drug resistant organisms such as Mycobacterium tuberculosis (Mtb) and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus -1 (HIV-1) and hepatitis B virus (HBV). The CRISPR/Cas9 system, which has revolutionized biomedical research, holds great promise for the identification and validation of novel drug targets...
November 16, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27855263/disruption-or-excision-of-provirus-as-an-approach-to-hiv-cure
#2
Keith R Jerome
An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27783955/a-cas9-ribonucleoprotein-platform-for-functional-genetic-studies-of-hiv-host-interactions-in-primary-human-t-cells
#3
Judd F Hultquist, Kathrin Schumann, Jonathan M Woo, Lara Manganaro, Michael J McGregor, Jennifer Doudna, Viviana Simon, Nevan J Krogan, Alexander Marson
New genetic tools are needed to understand the functional interactions between HIV and human host factors in primary cells. We recently developed a method to edit the genome of primary CD4(+) T cells by electroporation of CRISPR/Cas9 ribonucleoproteins (RNPs). Here, we adapted this methodology to a high-throughput platform for the efficient, arrayed editing of candidate host factors. CXCR4 or CCR5 knockout cells generated with this method are resistant to HIV infection in a tropism-dependent manner, whereas knockout of LEDGF or TNPO3 results in a tropism-independent reduction in infection...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27755113/new-research-on-using-crispr-cas9-to-treat-hiv
#4
Kristin Nicole Harper
No abstract text is available yet for this article.
October 14, 2016: AIDS
https://www.readbyqxmd.com/read/27736664/crispr-cas9-system-and-its-applications-in-human-hematopoietic-cells
#5
REVIEW
Xiaotang Hu
Since 2012, the CRISPR-Cas9 system has been quickly and successfully tested in a broad range of organisms and cells including hematopoietic cells. The application of CRISPR-Cas9 in human hematopoietic cells mainly involves the genes responsible for HIV infection, β-thalassemia and sickle cell disease (SCD). The successful disruption of CCR5 and CXCR4 genes in T cells by CRISPR-Cas9 promotes the prospect of the technology in the functional cure of HIV. More recently, eliminating CCR5 and CXCR4 in induced pluripotent stem cells (iPSCs) derived from patients and targeting the HIV genome have been successfully carried out in several laboratories...
November 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/27698388/the-variances-of-sp1-and-nf-%C3%AE%C2%BAb-elements-correlate-with-the-greater-capacity-of-chinese-hiv-1-b-ltr-for-driving-gene-expression
#6
Di Qu, Chuan Li, Feng Sang, Qiang Li, Zhi-Qiang Jiang, Li-Ran Xu, Hui-Jun Guo, Chiyu Zhang, Jian-Hua Wang
The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27624129/activation-of-the-dna-damage-response-is-a-conserved-function-of-hiv-1-and-hiv-2-vpr-that-is-independent-of-slx4-recruitment
#7
Oliver I Fregoso, Michael Emerman
UNLABELLED: There has been extraordinary progress in understanding the roles of lentiviral accessory proteins in antagonizing host antiviral defense proteins. However, the precise primary function of the accessory gene Vpr remains elusive. Here we suggest that engagement with the DNA damage response is an important function of primate lentiviral Vpr proteins because of its conserved function among diverse lentiviral lineages. In contrast, we show that, for HIV-1, HIV-2, and related Vpr isolates and orthologs, there is a lack of correlation between DNA damage response activation and interaction with the host SLX4 protein complex of structure specific endonucleases; some Vpr proteins are able to interact with SLX4, but the majority are not...
September 13, 2016: MBio
https://www.readbyqxmd.com/read/27594566/the-crispr-cas-system-from-bacterial-immunity-to-genome-engineering
#8
Maria Czarnek, Joanna Bereta
Precise and efficient genome modifications present a great value in attempts to comprehend the roles of particular genes and other genetic elements in biological processes as well as in various pathologies. In recent years novel methods of genome modification known as genome editing, which utilize so called "programmable" nucleases, came into use. A true revolution in genome editing has been brought about by the introduction of the CRISP-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) system, in which one of such nucleases, i...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27570612/antibodies-inside-of-a-cell-can-change-its-outside-can-intrabodies-provide-a-new-therapeutic-paradigm
#9
REVIEW
Andrea L J Marschall, Stefan Dübel
Challenges posed by complex diseases such as cancer, chronic viral infections, neurodegenerative disorders and many others have forced researchers to think beyond classic small molecule drugs, exploring new therapeutic strategies such as therapy with RNAi, CRISPR/Cas9 or antibody therapies as single or as combination therapies with existing drugs. While classic antibody therapies based on parenteral application can only reach extracellular targets, intracellular application of antibodies could provide specific advantages but is so far little recognized in translational research...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27528385/negative-feedback-regulation-of-hiv-1-by-gene-editing-strategy
#10
Rafal Kaminski, Yilan Chen, Julian Salkind, Ramona Bella, Won-Bin Young, Pasquale Ferrante, Jonathan Karn, Thomas Malcolm, Wenhui Hu, Kamel Khalili
The CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27404981/host-double-strand-break-repair-generates-hiv-1-strains-resistant-to-crispr-cas9
#11
Kristine E Yoder, Ralf Bundschuh
CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27389633/corrigendum-elimination-of-hiv-1-genomes-from-human-t-lymphoid-cells-by-crispr-cas9-gene-editing
#12
Rafal Kaminski, Yilan Chen, Tracy Fischer, Ellen Tedaldi, Alessandro Napoli, Yonggang Zhang, Jonathan Karn, Wenhui Hu, Kamel Khalili
No abstract text is available yet for this article.
2016: Scientific Reports
https://www.readbyqxmd.com/read/27341108/targeted-hiv-1-latency-reversal-using-crispr-cas9-derived-transcriptional-activator-systems
#13
Julia K Bialek, Gábor A Dunay, Maike Voges, Carola Schäfer, Michael Spohn, Rolf Stucka, Joachim Hauber, Ulrike C Lange
CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs), act indirectly through cellular pathways to induce viral transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27279606/complex-interplay-between-hiv-1-capsid-and-mx2-independent-alpha-interferon-induced-antiviral-factors
#14
Lorenzo Bulli, Luis Apolonia, Juliane Kutzner, Darja Pollpeter, Caroline Goujon, Nikolas Herold, Sarah-Marie Schwarz, Yannick Giernat, Oliver T Keppler, Michael H Malim, Torsten Schaller
UNLABELLED: Type I interferons (IFNs), including IFN-α, upregulate an array of IFN-stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined...
August 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27278725/anti-hiv-1-potency-of-the-crispr-cas9-system-insufficient-to-fully-inhibit-viral-replication
#15
Shuhei Ueda, Hirotaka Ebina, Yuka Kanemura, Naoko Misawa, Yoshio Koyanagi
The range of genome-editing tools has recently been expanded. In particular, an RNA-guided genome-editing tool, the clustered regularly interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, has many applications for human diseases. In this study, guide RNA (gRNA) to target gag, pol and a long terminal repeat of HIV-1 was designed and used to generate gRNA-expressing lentiviral vectors. An HIV-1-specific gRNA and Cas9 were stably dually transduced into a highly HIV-1-susceptible human T-cell line and the inhibitory ability of the anti-HIV-1 CRISPR/Cas9 lentiviral vector assessed...
July 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27230886/crispr-cas9-a-double-edged-sword-when-used-to-combat-hiv-infection
#16
Chen Liang, Mark A Wainberg, Atze T Das, Ben Berkhout
No abstract text is available yet for this article.
2016: Retrovirology
https://www.readbyqxmd.com/read/27194423/excision-of-hiv-1-dna-by-gene-editing-a-proof-of-concept-in-vivo-study
#17
R Kaminski, R Bella, C Yin, J Otte, P Ferrante, H E Gendelman, H Li, R Booze, J Gordon, W Hu, K Khalili
A CRISPR/Cas9 gene editing strategy has been remarkable in excising segments of integrated HIV-1 DNA sequences from the genome of latently infected human cell lines and by introducing InDel mutations, suppressing HIV-1 replication in patient-derived CD4+ T-cells, ex vivo. Here, we employed a short version of the Cas9 endonuclease, saCas9, together with a multiplex of guide RNAs (gRNAs) for targeting the viral DNA sequences within the 5'-LTR and the Gag gene for removing critically important segments of the viral DNA in transgenic mice and rats encompassing the HIV-1 genome...
August 2016: Gene Therapy
https://www.readbyqxmd.com/read/27183329/samhd1-controls-cell-cycle-status-apoptosis-and-hiv-1-infection-in-monocytic-thp-1-cells
#18
Serena Bonifati, Michele B Daly, Corine St Gelais, Sun Hee Kim, Joseph A Hollenbaugh, Caitlin Shepard, Edward M Kennedy, Dong-Hyun Kim, Raymond F Schinazi, Baek Kim, Li Wu
SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout...
August 2016: Virology
https://www.readbyqxmd.com/read/27139312/recent-advances-in-crispr-cas9-technology-for-targeting-latent-hiv-1-reservoirs
#19
Stacey C Tobin
No abstract text is available yet for this article.
July 17, 2016: AIDS
https://www.readbyqxmd.com/read/27068471/crispr-cas9-derived-mutations-both-inhibit-hiv-1-replication-and-accelerate-viral-escape
#20
Zhen Wang, Qinghua Pan, Patrick Gendron, Weijun Zhu, Fei Guo, Shan Cen, Mark A Wainberg, Chen Liang
Cas9 cleaves specific DNA sequences with the assistance of a programmable single guide RNA (sgRNA). Repairing this broken DNA by the cell's error-prone non-homologous end joining (NHEJ) machinery leads to insertions and deletions (indels) that often impair DNA function. Using HIV-1, we have now demonstrated that many of these indels are indeed lethal for the virus, but that others lead to the emergence of replication competent viruses that are resistant to Cas9/sgRNA. This unexpected contribution of Cas9 to the development of viral resistance is facilitated by some indels that are not deleterious for viral replication, but that are refractory to recognition by the same sgRNA as a result of changing the target DNA sequences...
April 19, 2016: Cell Reports
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