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Journal of Gene Medicine

Monika Rak, Anna Ochałek, Ewa Bielecka, Joanna Latasiewicz, Katarzyna Gawarecka, Jolanta Sroka, Jarosław Czyż, Katarzyna Piwowarczyk, Marek Masnyk, Marek Chmielewski, Tadeusz Chojnacki, Ewa Swiezewska, Zbigniew Madeja
BACKGROUND: One of the major challenges limiting development of gene therapy is absence of efficient and safe gene carriers. Among the non-viral gene delivery methods, lipofection is considered as one of the most promising. In this study a set of cationic polyprenyl derivatives (trimethylpolyprenylammonium iodides - PTAI) with different lengths of polyprenyl chains (from 7, 8 and 11 to 15 isoprene units) was suggested as a component of efficient DNA vehicles. METHODS: Optimization studies were conducted for PTAI in combination with co-lipid DOPE (dioleoylphosphatidylethanolamine) on DU145 human prostate cancer cells using: size and zeta potential measurements, confocal microscopy, fluorescein diacetate/ethidium bromide test, cell counting, time-lapse monitoring of cell movement, gap junctional intracellular coupling analysis, antimicrobial activity assay, red blood cell hemolysis test...
October 5, 2016: Journal of Gene Medicine
Hena Khalique, Jorge López Marco, Filip Lim
BACKGROUND: Although Herpes Simplex Virus Type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of about 15.4 kilobases of DNA sequences which are duplicated in the HSV-1 genome, complicating vector construction and stability. METHODS: As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired...
September 27, 2016: Journal of Gene Medicine
Laleh Shariati, Hossein Khanahmad, Mansoor Salehi, Zahra Hejazi, Ilnaz Rahimmaesh, Mohammad Amin Tabatabaiefar, Mohammad Hossein Modarressi
BACKGROUND: β-thalassemia is a major group of human genetic disorders which involves decrease or cease in the normal synthesis of the β-globin chains of hemoglobin. KLF1 is a key regulatory molecule involved in the γ to β-globin gene switching process directly inducing the expression of beta globin gene and indirectly repressing gamma globin. This study was performed to investigate the ability of an engineered CRISPR/Cas9 system to disrupt the KLF1 gene to inhibit the γ to β hemoglobin switching process in K562 cells...
September 26, 2016: Journal of Gene Medicine
Tianbo Jin, Hongxing Zhang, Qi Yang, Lei Li, Yongri Ouyang, Min Yang, Fengjiao Wang, Zhenyuan Wang, Ji Zhang, Dongya Yuan
BACKGROUND: The number of heroin addicts is increasing in the world. The environmental and genetic factors both play critical roles in the process of heroin addiction. We sought to investigate the associations between single nucleotide polymorphisms (SNPs) in LIN7C, BDNFOS and BDNF genes and drug addiction in the Han Chinese population. METHODS: We conducted a case-control study among 692 cases and 700 healthy controls from Xi'an, China. Eight SNPs were selected and genotyped using Sequenom Mass-ARRAY technology...
September 19, 2016: Journal of Gene Medicine
Xiaohui Lin, Jihong Wang, Lixia Yun, Shuhong Jiang, Langen Li, Xiaohai Chen, Zhen Li, Qiang Lu, Yihui Zhang, Xiaocheng Ma
BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. The objective of this study was to identify a possible connection between gene polymorphisms and the risk of developing DR. MATERIALS AND METHODS: A total of 319 patients with Type 2 Diabetes mellitus (T2DM) were selected. All patients underwent a complete eye examination. Based on this, the patients with T2DM were divided into two subgroups: 175 patients with retinopathy (DR) and 144 patients without retinopathy (NDR)...
September 8, 2016: Journal of Gene Medicine
Kenji Kokura, Yasushi Kuromi, Takeshi Endo, Naohiko Anzai, Yasuhiro Kazuki, Mitsuo Oshimura, Tetsuya Ohbayashi
BACKGROUND: Kidney injury molecule-1 (Kim-1) has been validated as a urinary biomarker for acute and chronic renal damage. The expression of Kim-1 mRNA is also activated by acute kidney injury induced by cisplatin in rodents and humans. To date, the measurement of Kim-1 expression has not fully allowed the detection of in vitro cisplatin nephrotoxicity in immortalized culture cells such as human kidney-2 cells and immortalized proximal tubular epithelial cells. METHODS: We measured the augmentation of Kim-1 mRNA expression after cisplatin addition using immortalized S3 cells established from the kidneys of transgenic mice harboring temperature-sensitive large T antigen from Simian virus 40...
September 3, 2016: Journal of Gene Medicine
Pratigya Gautam, Robert D Foale, Asha Recino, Jing Zhao, Shu Uin Gan, Maja Wallberg, Roy Calne, Andrew M L Lever
BACKGROUND: The lack of an ideal cell type that can be easily acquired, modified to produce insulin, and re-implanted has been a limitation for ex vivo insulin gene therapy. Canine diabetes is currently treated with human insulin and is a good model for human diabetes. Mesenchymal stromal cells (MSCs) are a promising candidate cell type for gene therapy. Here we optimised insulin production using lentiviral transduced canine MSCs aiming to evaluate their ability for use as surrogate beta cells...
August 30, 2016: Journal of Gene Medicine
Xiaoyan Zheng, Yifei Lv, Shuang Li, Qiannan Zhang, Xueting Zhang, Zhiming Hao
BACKGROUND AND AIMS: Extracellular high mobility group box 1 (HMGB1) is crucially implicated in the pathogenesis of inflammatory bowel diseases (IBDs). A box domain of HMGB1 has been identified as a specific antagonist of HMGB1. In this study, we tested the effects of adeno-associated virus (AAV)-mediated colonic secretory expression of HMGB1 A box on murine experimental colitis. METHODS: Self-complementary AAV-2 carrying mouse IgGk leader-human HMGB1 A box (AAV-HMGB1 A box) was constructed...
August 30, 2016: Journal of Gene Medicine
Jie Jin, Yu Wang, Yang Xu, Xu Zhou, Yu Liu, Xiang Li, Jin Wang
BACKGROUND: In this study, we explored the functional roles of microRNA-144 (miR-144) upregulation and downregulation in human acute lymphoblastic leukemia (ALL). METHOD: Gene expression of miR-144 was examined by qRT-PCR in both ALL cell lines and T-leukemic cells of ALL patients. In ALL cell lines Molt-3 and Jurkat cells, miR-144 was either upregulated or downregulated through lentiviral transduction. The subsequent effects of miR-144 upregulation or downregulation on ALL proliferation, cell-cycle transition, and in vivo xenograft were assessed...
August 24, 2016: Journal of Gene Medicine
Yongjun He, Xiyang Zhang, Xun Li, Jieli Du, Xue He, Zhiying Zhang, Yuan Zhang, Longli Kang, Tianbo Jin, Dongya Yuan
BACKGROUND: High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea-level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE...
September 2016: Journal of Gene Medicine
HariOm Singh, Shruti D Marathe, Vijay Nema, Manisha V Ghate, Raman R Gangakhedkar
BACKGROUND: Astrocytes are susceptible to HIV-1 infection. Neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Therefore, we evaluated the association of MMP-2(-735C > T) and MMP-9(-1562C > T) polymorphisms with respect to the susceptibility of developing HIV-associated neurocognitive disorders (HAND) and its severity. METHODS: We enrolled 50 HIV-infected individuals with HAND, 130 without HAND and 150 unrelated healthy controls...
September 2016: Journal of Gene Medicine
Jubayer A Hossain, Lars Rømo Ystaas, Jelena Mrdalj, Kristjan Välk, Kristoffer Riecken, Boris Fehse, Rolf Bjerkvig, Janne Grønli, Hrvoje Miletic
BACKGROUND: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation. METHODS: In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study...
September 2016: Journal of Gene Medicine
Lyudmila S Krassikova, Saida S Karshieva, Ivan B Cheglakov, Alexander V Belyavsky
BACKGROUND: The combination of stem cell-based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue-derived mesenchymal stem cells (AT-MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC). METHODS: Adipose tissue-derived mesenchymal stem cells were transfected with non-insert plasmid construct transiently expressing fused cytosine deaminase-uracil phosphoribosyltransferase protein (CDA/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA/UPRT/VP22)...
September 2016: Journal of Gene Medicine
Xiaoyuan Jia, Yongyi Chen, Xin Zhao, Chunwei Lv, Jie Yan
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal malignancy. Vaccinia virus (VV) possessed many inherent advantages with respect to being engineered as a vector for cancer gene therapy, although the mechanism of action remains to be explored further. METHODS: We constructed a thymidine kinase gene insertional inactivated VV, named VV-Onco, and then tested its effects on cell viability, apoptosis and colony formation ability in a highly metastatic human hepatocellular carcinoma cell line MHCC97-H, and also investigated the potential cell signal pathways involved in this action...
September 2016: Journal of Gene Medicine
Volker M Betz, Oliver B Betz, Tom Rosin, Alexander Keller, Christian Thirion, Michael Salomon, Suzanne Manthey, Peter Augat, Volkmar Jansson, Peter E Müller, Stefan Rammelt, Hans Zwipp
BACKGROUND: Delivery of bone morphogenetic protein-7 (BMP-7) to bone defects can be improved by applying gene transfer methods. However, traditional ex vivo gene therapy approaches are cumbersome and costly, requiring the extraction and culturing of cells. Therefore, we evaluated a novel, expedited ex vivo BMP-7 gene transfer technology based on the use of fragments of subcutaneous fat tissue. METHODS: We created 5-mm mid-femoral bone defects in the right femora of 23 male, syngeneic Fischer 344 rats...
August 2016: Journal of Gene Medicine
Daisuke Sotobayashi, Hirohisa Kawahata, Natsuki Anada, Toshio Ogihara, Ryuichi Morishita, Motokuni Aoki
BACKGROUND: Limited range of motion (ROM) as a result of joint contracture in treatment associated with joint immobilization or motor paralysis is a critical issue. However, its molecular mechanism has not been fully clarified and a therapeutic approach is not yet established. METHODS: In the present study, we investigated its molecular mechanism, focusing on the role of a transcription factor, hypoxia inducible factor-1 (HIF-1), which regulates the expression of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF), and evaluated the possibility of molecular therapy to inhibit HIF-1 activation by ribbon-type decoy oligonucleotides (ODNs) for HIF-1 using immobilized knee animal models...
August 2016: Journal of Gene Medicine
Xiu-Feng Huang, Yuqin Wang, Fen-Fen Li, Dan Lin, Ma-Li Dai, Qing-Feng Wang, Zi-Bing Jin
BACKGROUND: Complement factor H (CFH) related proteins (CFHRs) play important roles in complement activation pathways, whereas previous studies have only shown that CFH can affect the development of uveitis. In the present study, we investigated the potential associations between one of single-nucleotide polymorphisms in the CFHR2 gene with acute anterior uveitis (AAU). METHODS: A total of 571 subjects, 283 patients diagnosed with AAU and 288 healthy adult controls, were recruited for this case-control study...
August 2016: Journal of Gene Medicine
Joanna Laskowska, Joanna Lewandowska-Bieniek, Joanna Szczepanek, Jan Styczyński, Andrzej Tretyn
BACKGROUND: A major problem in the treatment of leukemia is the development of drug resistance to chemotherapeutic agents. METHODS: To determine the ex vivo drug resistance profile to anthracyclines, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay was performed on mononuclear cells obtained from 155 patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). Gene expression profiles (for 51 patients with ALL and 16 with AML) were prepared on the basis of cRNA hybridization to oligonucleotide arrays of the human genome (Affymetrix)...
August 2016: Journal of Gene Medicine
Simone Gabner, Juraj Hlavaty, Karsten Velde, Matthias Renner, Florien Jenner, Monika Egerbacher
BACKGROUND: Osteoarthritis, a chronic and progressive degenerative joint disorder, ranks amongst the top five causes of disability. Given the high incidence, associated socioeconomic costs and the absence of effective disease-modifying therapies of osteoarthritis, cell-based treatments offer a promising new approach. Owing to their paracrine, differentiation and self-renewal abilities, mesenchymal stem cells (MSCs) have great potential for regenerative medicine, which might be further enhanced by targeted gene therapy...
August 2016: Journal of Gene Medicine
Hongxing Zhang, Qi Yang, Wenkai Zheng, Yongri Ouyang, Min Yang, Fengjiao Wang, Tianbo Jin, Ji Zhang, Zhenyuan Wang
BACKGROUND: There is growing evidence that genetic factors also contribute to drug addiction. The human cytochrome P450 has shown special interest because of pharmacokinetic variation in different individuals and populations, which is largely determined by the relevant genes. The present study aimed to investigate the polymorphism of the CYP/addicts relationship. METHODS: We genotyped 13 tag single-nucleotide polymorphisms (tSNPs) from three genes, including 692 cases and 700 controls...
August 2016: Journal of Gene Medicine
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