Development of a self-inactivating lentivirus vector. (1998)

by H Miyoshi, U Blomer, M Takahashi, F H Gage, I M Verma
Venue:J. Virol.
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Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer

by Masayo Takahashi, Hiroyuki Miyoshi, Inder M. Verma, Fred H. Gage, Masayo Takahashi, Hiroyuki Miyoshi, Inder M. Verma, Fred, H. Gage - J , 1999
"... These include: This article cites 35 articles, 22 of which can be accessed free at: ..."
Abstract - Cited by 27 (2 self) - Add to MetaCart
These include: This article cites 35 articles, 22 of which can be accessed free at:
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Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One 2009

by Erika L. Spaeth, Jennifer L. Dembinski, A. Kate Sasser, Keri Watson, Brett Hall, Michael Andreeff, Frank Marini
"... Background: Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesis as matrix synthesizing or matrix degrading cells, contrac ..."
Abstract - Cited by 17 (1 self) - Add to MetaCart
Background: Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesis as matrix synthesizing or matrix degrading cells, contractile cells, and even blood vessel associated cells. The production of growth factors, cytokines, chemokines, matrix-degrading enzymes, and immunomodulatory mechanisms by these cells augment tumor progression by providing a suitable environment. There are several suggested origins of the TAF including tissue-resident, circulating, and epithelial-to-mesenchymal-transitioned cells. Methodology/Principal Findings: We provide evidence that TAF are derived from mesenchymal stem cells (MSC) that acquire a TAF phenotype following exposure to or systemic recruitment into adenocarcinoma xenograft models including breast, pancreatic, and ovarian. We define the MSC derived TAF in a xenograft ovarian carcinoma model by the immunohistochemical presence of 1) fibroblast specific protein and fibroblast activated protein; 2) markers phenotypically associated with aggressiveness, including tenascin-c, thrombospondin-1, and stromelysin-1; 3) production of pro-tumorigenic growth factors including hepatocyte growth factor, epidermal growth factor, and interleukin-6; and 4) factors indicative of vascularization, including alpha-smooth muscle actin, desmin, and vascular endothelial growth factor. We demonstrate that under long-term tumor conditioning in vitro, MSC express TAF–like proteins. Additionally, human MSC but
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Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes. PLoS One 3: e3474

by Feng Cao, Roger A. Wagner, Kitchener D. Wilson, Xiaoyan Xie, Ji-dong Fu, Micha Drukker, Andrew Lee, Ronald A. Li, Sanjiv S. Gambhir, Irving L. Weissman, Robert C. Robbins, Joseph C , 2008
"... Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injur ..."
Abstract - Cited by 17 (2 self) - Add to MetaCart
Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies
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Generation of transgenic non-human primates with germline transmission.

by Erika Sasaki , Hiroshi Suemizu , Akiko Shimada , Kisaburo Hanazawa , Ryo Oiwa , Michiko Kamioka , Ikuo Tomioka , Yusuke Sotomaru , Reiko Hirakawa , Tomoo Eto , Seiji Shiozawa , Takuji Maeda , Mamoru Ito , Ryoji Ito , Chika Kito , Chie Yagihashi , Kenji Kawai , Hiroyuki Miyoshi , Yoshikuni Tanioka , Norikazu Tamaoki , Sonoko Habu , Hideyuki Okano , Tatsuji Nomura - Nature , 2009
"... The common marmoset (Callithrix jacchus) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to p ..."
Abstract - Cited by 17 (2 self) - Add to MetaCart
The common marmoset (Callithrix jacchus) is increasingly attractive for use as a non-human primate animal model in biomedical research. It has a relatively high reproduction rate for a primate, making it potentially suitable for transgenic modification. Although several attempts have been made to produce non-human transgenic primates, transgene expression in the somatic tissues of live infants has not been demonstrated by objective analyses such as polymerase chain reaction with reverse transcription or western blots. Here we show that the injection of a self-inactivating lentiviral vector in sucrose solution into marmoset embryos results in transgenic common marmosets that expressed the transgene in several organs. Notably, we achieved germline transmission of the transgene, and the transgenic offspring developed normally. The successful creation of transgenic marmosets provides a new animal model for human disease that has the great advantage of a close genetic relationship with humans. This model will be valuable to many fields of biomedical research.

Development of multigene and regulated lentivirus vectors

by Jakob Reiser, Zhennan Lai, Xian-yang Zhang, O. Brady, Jakob Reiser, Zhennan Lai, Xian-yang Zhang, Roscoe O. Brady - J , 2000
"... These include: This article cites 67 articles, 37 of which can be accessed free at: ..."
Abstract - Cited by 11 (2 self) - Add to MetaCart
These include: This article cites 67 articles, 37 of which can be accessed free at:
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Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis. Toxicol Sci 2005;88:367–374

by Shin-ichiro Sugiyama, Naoyuki Shimada, Hiroyuki Miyoshi, Kiyoshi Yamauchi
"... SIN, self-inactivating; LV, lentivirus vector; TRE, TH-response element; T3, 3,3’,5-L-triiodothyronine; T4, L-thyroxine; Triac, 3,3’5-L-triiodothyroacetic acid; D-T3, 3,3’,5-D-triiodothyronine; rT3, ..."
Abstract - Cited by 9 (0 self) - Add to MetaCart
SIN, self-inactivating; LV, lentivirus vector; TRE, TH-response element; T3, 3,3’,5-L-triiodothyronine; T4, L-thyroxine; Triac, 3,3’5-L-triiodothyroacetic acid; D-T3, 3,3’,5-D-triiodothyronine; rT3,
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Lentiviral Vif degrades the APOBEC3Z3/APOBEC3H protein of its mammalian host and is capable of cross-species activity

by Rebecca S. Larue, Joy Lengyel, Reuben S. Harris - 2013 by the authors; licensee MDPI
"... All lentiviruses except equine infectious anemia virus (EIAV) use the small accessory protein Vif to coun-teract the restriction activity of the relevant APOBEC3 (A3) proteins of their host species. Prior studies have suggested that the Vif-A3 interaction is species specific. Here, using the APOBEC3 ..."
Abstract - Cited by 7 (1 self) - Add to MetaCart
All lentiviruses except equine infectious anemia virus (EIAV) use the small accessory protein Vif to coun-teract the restriction activity of the relevant APOBEC3 (A3) proteins of their host species. Prior studies have suggested that the Vif-A3 interaction is species specific. Here, using the APOBEC3H (Z3)-type proteins from five distinct mammals, we report that this is generally not the case: some lentiviral Vif proteins are capable of triggering the degradation of both the A3Z3-type protein of their normal host species and those of several other mammals. For instance, SIVmac Vif can mediate the degradation of the human, macaque, and cow A3Z3-type proteins but not of the sheep or cat A3Z3-type proteins. Maedi-visna virus (MVV) Vif is similarly promiscuous, degrading not only sheep A3Z3 but also the A3Z3-type proteins of humans, macaques, cows, and cats. In contrast to the neutralization capacity of these Vif proteins, human immunodeficiency virus (HIV), bovine immunodeficiency virus (BIV), and feline immunodeficiency virus (FIV) Vif appear specific to the A3Z3-type protein of their hosts. We conclude, first, that the Vif-A3Z3 interaction can be promiscuous and, second, despite this tendency, that each lentiviral Vif protein is optimized to degrade the A3Z3 protein of its mam-malian host. Our results thereby suggest that the Vif-A3Z3 interaction is relevant to lentivirus biology. Lentiviruses are a unique class of complex retroviruses that encode a variety of accessory proteins in addition to the re-
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Integrated Self-Inactivating Lentiviral Vectors Produce Full-Length Genomic Transcripts Competent for Encapsidation and Integration

by Aaron C. Logan, Dennis L. Haas, Tal Kafri, Donald B. Kohn , 2004
"... To make human immunodeficiency virus type 1 (HIV-1)-based vectors safer for use in the research and clinical setting, a significant modification to the HIV-1 genome has been the deletion of promoter and enhancer elements from the U3 region of the long terminal repeat (LTR). Vectors containing this d ..."
Abstract - Cited by 6 (1 self) - Add to MetaCart
To make human immunodeficiency virus type 1 (HIV-1)-based vectors safer for use in the research and clinical setting, a significant modification to the HIV-1 genome has been the deletion of promoter and enhancer elements from the U3 region of the long terminal repeat (LTR). Vectors containing this deletion are thought to have no LTR-directed transcription and are called self-inactivating (SIN) lentivectors. Using four distinct approaches, we show that SIN lentivectors continue to have promoter activity near the 5 � LTR, which is responsible for the production of full-length vector transcripts. To verify that transcripts derived from the LTR in SIN lentivectors are competent for encapsidation and integration, we transduced a lentiviral packaging cell line with a SIN lentivector and then observed the production of viable vector particles containing full-length SIN lentivector genomes. We have also attempted to identify sequences in the SIN lentivector which are responsible for transcriptional activation at the 5 � LTR. Using different segments of the vector LTR and leader region in a promoter assay, we have determined that the residual promoter activity is contained entirely within the leader region and that, although this element is downstream of the transcription initiation site, it is capable of initiating transcription from the 5 � end of R in the LTR. Mutation of leader region binding sites for the transcriptional activators downstream binding factor 1 (DBF1) and SP1 reduces transcription from the SIN LTR by up to 80%. Knowledge of the potential for mobilization of HIV-1-derived SIN lentivectors will be
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Targeted Transgene Expression in Müller Glia of Normal and Diseased Retinas Using Lentiviral Vectors

by Kenneth P. Greenberg, Scott F. Geller, David V. Schaffer, John G. Flannery
"... PURPOSE. Müller glia play crucial roles in retinal homeostasis and function. Genetic modification of Müller cells by viral gene delivery would be valuable for studies of their normal physiology and roles in retinal disease states. However, stable and efficient transgene expression in Müller cells af ..."
Abstract - Cited by 5 (3 self) - Add to MetaCart
PURPOSE. Müller glia play crucial roles in retinal homeostasis and function. Genetic modification of Müller cells by viral gene delivery would be valuable for studies of their normal physiology and roles in retinal disease states. However, stable and efficient transgene expression in Müller cells after delivery of gene transfer vectors has remained elusive. Transcriptional and transductional targeting approaches were used to engineer recombinant HIV-1-based lentiviral (LV) vectors capable of highly efficient and sustained Müller cell transgene expression in healthy and diseased rodent retinas. METHODS. Expression cassettes containing glia-specific promoters (CD44, glial fibrillary acidic protein, and vimentin) and an enhanced green fluorescent protein (eGFP) cDNA were cloned into LV backbones, which were packaged into infectious vector particles displaying either the vesicular stomatitis virus

Establishment of Functioning Human Corneal Endothelial Cell Line with High Growth Potential

by Tadashi Yokoi, Yuko Seko, Tae Yokoi, Hatsune Makino, Shin Hatou, Masakazu Yamada, Akihiro Umezawa, Hiroshi Nishina, Noriyuki Azuma
"... Hexagonal-shaped human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na +- and K +-dependent ATPa ..."
Abstract - Cited by 4 (0 self) - Add to MetaCart
Hexagonal-shaped human corneal endothelial cells (HCEC) form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na +- and K +-dependent ATPase (Na + /K +-ATPase). Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs) in the Rb pathway (p16-CDK4/CyclinD1-pRb). In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7)) and transduced human corneal endothelial cell by Cdk4R24C/ CyclinD1 (THCEH (Cyclin)). Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7), THCEH (Cyclin) and non-transduced HCEC, but cell cycle-related genes were upregulated in THCEC (E6/E7) and THCEH (Cyclin). THCEH (Cyclin) expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na + /K +-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7). This
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