scholarly journals Preclinical safety and efficacy of an anti–HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor

2014 ◽  
Vol 1 ◽  
pp. 11 ◽  
Author(s):  
Orit Wolstein ◽  
Maureen Boyd ◽  
Michelle Millington ◽  
Helen Impey ◽  
Joshua Boyer ◽  
...  
Keyword(s):  
Lentiviral Vector ◽  
Short Hairpin Rna ◽  
Fusion Inhibitor ◽  
Hairpin Rna ◽  
Safety And Efficacy ◽  
Short Hairpin ◽  
Anti Hiv ◽  
Preclinical Safety ◽  
Hiv 1

scholarly journals A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1534-1544 ◽  
Author(s):  
Saki Shimizu ◽  
Patrick Hong ◽  
Balamurugan Arumugam ◽  
Lauren Pokomo ◽  
Joshua Boyer ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Lentiviral Vector ◽  
Short Hairpin Rna ◽  
Lymphoid Organs ◽  
Great Promise ◽  
Ccr5 Expression ◽  
Hairpin Rna ◽  
Short Hairpin ◽  
Hiv 1

AbstractInhibiting the expression of the HIV-1 coreceptor CCR5 holds great promise for controlling HIV-1 infection in patients. Here we report stable knockdown of human CCR5 by a short hairpin RNA (shRNA) in a humanized bone marrow/liver/thymus (BLT) mouse model. We delivered a potent shRNA against CCR5 into human fetal liver-derived CD34+ hematopoietic progenitor/stem cells (HPSCs) by lentiviral vector transduction. We transplanted vector-transduced HPSCs solidified with Matrigel and a thymus segment under the mouse kidney capsule. Vector-transduced autologous CD34+ cells were subsequently injected in the irradiated mouse, intended to create systemic reconstitution. CCR5 expression was down-regulated in human T cells and monocytes/macrophages in systemic lymphoid tissues, including gut-associated lymphoid tissue, the major site of HIV-1 replication. The shRNA-mediated CCR5 knockdown had no apparent adverse effects on T-cell development as assessed by polyclonal T-cell receptor Vβ family development and naive/memory T-cell differentiation. CCR5 knockdown in the secondary transplanted mice suggested the potential of long-term hematopoietic reconstitution by the shRNA-transduced HPSCs. CCR5 tropic HIV-1 infection was effectively inhibited in mouse-derived human splenocytes ex vivo. These results demonstrate that lentiviral vector delivery of shRNA into human HPSCs could stably down-regulate CCR5 in systemic lymphoid organs in vivo.

Lentiviral vector delivery of short hairpin RNA to NG2 and neurotrophin-3 promotes locomotor recovery in injured rat spinal cord

Cytotherapy ◽  
2012 ◽  
Vol 14 (10) ◽  
pp. 1235-1244 ◽  
Author(s):  
Eleanor M. Donnelly ◽  
Nicolas N. Madigan ◽  
Gemma E. Rooney ◽  
Andrew Knight ◽  
Bingkun Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Lentiviral Vector ◽  
Short Hairpin Rna ◽  
Rat Spinal Cord ◽  
Hairpin Rna ◽  
Locomotor Recovery ◽  
Neurotrophin 3 ◽  
Short Hairpin ◽  
Vector Delivery

scholarly journals Clearance of Measles Virus from Persistently Infected Cells by Short Hairpin RNA

2009 ◽  
Vol 83 (18) ◽  
pp. 9423-9431 ◽  
Author(s):  
Michael Zinke ◽  
Sabine Kendl ◽  
Katrin Singethan ◽  
Markus Fehrholz ◽  
Dajana Reuter ◽  
...  
Keyword(s):  
Measles Virus ◽  
Fluorescent Protein ◽  
Lentiviral Vector ◽  
Test System ◽  
Short Hairpin Rna ◽  
Hairpin Rna ◽  
Persistently Infected ◽  
Infected Cells ◽  
Short Hairpin ◽  
Nt2 Cells

ABSTRACT Subacute sclerosing panencephalitis (SSPE) is a demyelinating central nervous system disease caused by a persistent measles virus (MV) infection of neurons and glial cells. There is still no specific therapy available, and in spite of an intact innate and adaptive immune response, SSPE leads inevitably to death. In order to select effective antiviral short interfering RNAs (siRNAs), we established a plasmid-based test system expressing the mRNA of DsRed2 fused with mRNA sequences of single viral genes, to which certain siRNAs were directed. siRNA sequences were expressed as short hairpin RNA (shRNA) from a lentiviral vector additionally expressing enhanced green fluorescent protein (EGFP) as an indicator. Evaluation by flow cytometry of the dual-color system (DsRed and EGFP) allowed us to find optimal shRNA sequences. Using the most active shRNA constructs, we transduced persistently infected human NT2 cells expressing virus-encoded HcRed (piNT2-HcRed) as an indicator of infection. shRNA against N, P, and L mRNAs of MV led to a reduction of the infection below detectable levels in a high percentage of transduced piNT2-HcRed cells within 1 week. The fraction of virus-negative cells in these cultures was constant over at least 3 weeks posttransduction in the presence of a fusion-inhibiting peptide (Z-Phe-Phe-Gly), preventing the cell fusion of potentially cured cells with persistently infected cells. Transduced piNT2 cells that lost HcRed did not fuse with underlying Vero/hSLAM cells, indicating that these cells do not express viral proteins any more and are “cured.” This demonstrates in tissue culture that NT2 cells persistently infected with MV can be cured by the transduction of lentiviral vectors mediating the long-lasting expression of anti-MV shRNA.

scholarly journals Lentiviral Vector-Mediated Delivery of Short Hairpin RNA Results in Persistent Knockdown of Gene Expression in Mouse Brain

2003 ◽  
Vol 14 (18) ◽  
pp. 1799-1807 ◽  
Author(s):  
Chris Van den Haute ◽  
Kristel Eggermont ◽  
Bart Nuttin ◽  
Zeger Debyser ◽  
Veerle Baekelandt
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Lentiviral Vector ◽  
Short Hairpin Rna ◽  
Hairpin Rna ◽  
Short Hairpin

scholarly journals Silencing of HIV-1 gag gene from epidemic strains among men who have sex with men (MSM) in Tianjin, China by a broad-spectrum short hairpin RNA

VirusDisease ◽  
2014 ◽  
Vol 25 (3) ◽  
pp. 294-301
Author(s):  
Zhipin Liang ◽  
Xin Wang ◽  
Hanmei Li ◽  
Bin Liu ◽  
Xuechao Zhao ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Short Hairpin Rna ◽  
Hairpin Rna ◽  
Short Hairpin ◽  
Sex With Men ◽  
Hiv 1

scholarly journals Engineering HIV-1-Resistant T-Cells from Short-Hairpin RNA-Expressing Hematopoietic Stem/Progenitor Cells in Humanized BLT Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e53492 ◽  
Author(s):  
Gene-Errol E. Ringpis ◽  
Saki Shimizu ◽  
Hubert Arokium ◽  
Joanna Camba-Colón ◽  
Maria V. Carroll ◽  
...  
Keyword(s):  
T Cells ◽  
Progenitor Cells ◽  
Short Hairpin Rna ◽  
Hairpin Rna ◽  
Hematopoietic Stem ◽  
Short Hairpin ◽  
Blt Mice ◽  
Hiv 1

An optimized lentiviral vector system for conditional RNAi and efficient cloning of microRNA embedded short hairpin RNA libraries

Biomaterials ◽  
2017 ◽  
Vol 139 ◽  
pp. 102-115 ◽  
Author(s):  
Felix F. Adams ◽  
Dirk Heckl ◽  
Thomas Hoffmann ◽  
Steven R. Talbot ◽  
Arnold Kloos ◽  
...  
Keyword(s):  
Lentiviral Vector ◽  
Short Hairpin Rna ◽  
Vector System ◽  
Hairpin Rna ◽  
Short Hairpin

scholarly journals Novel Pol II Fusion Promoter Directs Human Immunodeficiency Virus Type 1-Inducible Coexpression of a Short Hairpin RNA and Protein

2006 ◽  
Vol 80 (4) ◽  
pp. 1863-1873 ◽  
Author(s):  
Hoshang J. Unwalla ◽  
Hai-Tang Li ◽  
Ingrid Bahner ◽  
Ming-Jie Li ◽  
Donald Kohn ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Expression System ◽  
Short Hairpin Rna ◽  
Wild Type ◽  
Hairpin Rna ◽  
Pol Ii ◽  
Novel Approach ◽  
Short Hairpin ◽  
Hiv 1

ABSTRACT We demonstrate a novel approach for coexpression of a short hairpin RNA (shRNA) with an open reading frame which exploits transcriptional read-through of a minimal polyadenylation signal from a Pol II promoter. We first observed efficient inducible expression of enhanced green fluorescent protein along with an anti-rev shRNA. We took advantage of this observation to test coexpression of the transdominant negative mutant (humanized) of human immunodeficiency type 1 (HIV-1) Rev (huRevM10) along with an anti-rev shRNA via an HIV-1-inducible fusion promoter. The coexpression of the shRNA and transdominant protein resulted in potent, long-term inhibition of HIV-1 gene expression and suppression of shRNA-resistant mutants. This dual expression system has broad-based potential for other shRNA applications, such as cases where simultaneous knockdown of mutant and wild-type transcripts must be accompanied by replacement of the wild-type protein.

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