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Journal of Gene Medicine

Mohamed Sharaf-Eldein, Doaa Elghannam, Camelia Abdel-Malak
OBJECTIVE: Macrophage inhibitory factor (MIF) is pro-inflammatory cytokine modulating monocyte motility and pleiotropic regulator of different biological and cellular processes. The MIF - 173G/C (rs755622) polymorphism is found in the promoter region and affect its activity. Our study is designed to investigate the MIF polymorphism as a risk factor for acute lymphoblastic leukemia (ALL) development in the Egyptian children. METHODS: We analyzed MIF - 173G/C (rs755622) polymorphism in 180 ALL cases and 150 healthy control children by amplification of the gene using Polymerase chain reaction (PCR) followed by restriction endonuclease digestion and running on agarose gel then visualization for the product...
July 11, 2018: Journal of Gene Medicine
Hanchao Li, Qian Li, Xueting Zhang, Xiaoyan Zheng, Qiannan Zhang, Zhiming Hao
AIM: To clarify the effects of thymosin β4 (Tβ4) on CCl4 -induced hepatic fibrosis in mice and further explore the underlying mechanisms. METHODS: Expression of Tβ4 in fibrotic liver tissues was assessed by real-time quantitative reverse transcriptase PCR (RQ-PCR) and immunohistochemistry (IHC). The effects of intraperitoneal adeno-associated virus-Tβ4 (AAV-Tβ4) on CCl4 -induced hepatic fibrosis were observed through the evaluation of collagen deposition, hepatic stellate cell (HSC) activation and pro-fibrotic cytokine expression...
July 4, 2018: Journal of Gene Medicine
Volker M Betz, Bin Ren, Carolin Messmer, Volkmar Jansson, Oliver B Betz, Peter E Müller
BACKGROUND: Bone morphogenetic protein-2 (BMP-2) gene activated muscle tissue fragments can regenerate large bone defects in preclinical animal models. The use of tissue fragments instead of isolated cells expedites gene-enhanced tissue engineering and may raise chances for clinical translation. The present in vitro study investigates whether the osteoinductive effect of BMP-2 on muscle tissue fragments can be enhanced by use of the heterodimers BMP-2/6 or BMP-2/7. METHODS: Skeletal muscle tissue fragments from rats were cultured in vitro for up to 20 days in normal medium, osteogenic medium, or osteogenic medium supplemented with either a low (50 ng/ml) or high (200 ng/ml) concentration of recombinant human BMP-2, BMP-2/6 or BMP-2/7...
June 28, 2018: Journal of Gene Medicine
Benjamin Steinborn, Ines Truebenbach, Stephan Morys, Ulrich Lächelt, Ernst Wagner, Wei Zhang
BACKGROUND: Developing new drug delivery carriers addressing chemoresistance is still full of challenges and opportunities. As the rapid development of small interfering RNA (siRNA) provides promising therapeutic perspectives, nanocarriers for drug and siRNA co-delivery present new alternatives for cancer therapy. METHODS: A co-delivery nanosystem for methotrexate (MTX) or gamma-glutamylated derivatives (gE2 -MTX and gE5 -MTX) and antitumoral EG5 siRNA has been developed utilizing the sequence defined cationic lipo-oligomers 454, 1021 and 1027...
June 27, 2018: Journal of Gene Medicine
Elizabeth M Everson, Jonah D Hocum, Grant D Trobridge
BACKGROUND: Previous studies have shown that foamy viral (FV) vectors are a promising alternative to gammaretroviral and lentiviral vectors and insulators can improve FV vector safety. However, in a previous analysis of insulator effects on FV vector safety, strong viral promoters were used to elicit genotoxic events. Here we developed and analyzed the efficacy and safety of a high-titer, clinically relevant FV vector driven by the housekeeping promoter elongation factor-1α and insulated with an enhancer blocking A1 insulator (FV-EGW-A1)...
June 23, 2018: Journal of Gene Medicine
Weihua Yuan, Jie Chen, Ying Cao, Lingcong Yang, Luxi Shen, Qi Bian, Shufang Bin, Panyuan Li, Jiawei Cao, Hezhi Fang, Haihua Gu, Hongzhi Li
BACKGROUND: The production of anti-Her2 chimeric antigen receptor (CAR) T cells needs to be optimized to make it a reliable therapy. METHODS: Three types of lentiviral vectors expressing anti-Her2 CAR together with packaging plasmids were co-transfected into 293 T-17 cells. The vector with the best packaging efficiency was selected, and the packaging cell culture system and packaging plasmid system were optimized. Centrifugation speed was optimized for the concentration of lentivirus stock...
May 30, 2018: Journal of Gene Medicine
Mark D Unger, Josef Pleticha, Lukas F Heilmann, Laura K Newman, Timothy P Maus, Andreas S Beutler
INTRODUCTION: Intrathecal interleukin (IL)-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, is a potential therapeutic for various human diseases, and was found to be nontoxic in dogs, when the human IL-10 ortholog was tested. However, recent studies in swine testing porcine IL-10 demonstrated fatal neurotoxicity. The present study aimed to deliver vector-encoded human IL-10 in swine, measure expression of the transgene in cerebrospinal fluid and monitor animals for signs of neurotoxicity...
May 25, 2018: Journal of Gene Medicine
Yunpeng Cai, Anna-Marie Makarova, Jesper Wengel, Kenneth A Howard
BACKGROUND: Antisense gapmer oligonucleotide drugs require delivery and biodistribution enabling technologies to increase in vivo efficacy. An attractive approach is their binding and consequent transport by the endogenous human serum albumin pool as mediated by fatty acid incorporation into the gapmer design. METHODS: The present study investigated the effect of palmitoyl modification and position on albumin-binding, cellular uptake and in vitro gene silencing of gapmers with either a phosphorothioate (PS) or phosphodiester (PO) backbone...
May 25, 2018: Journal of Gene Medicine
Guo Ai, Weiming Yan, Haijing Yu, Fang Xiao, Dong Xi, Ke Ma, Jiaquan Huang, Xiaoping Luo, Xiaoyang Wan, Qin Ning
BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory disease caused by an aberrant immune response to hepatic self-antigens in which regulatory T cells (Tregs) are critical for maintaining immunosupression. The soluble form of fibrinogen-like protein 2 (sFGL2), a novel effector molecule of Treg, is rarely investigated in AIH. In the present study, we dissected the role of sFGL2 in autoimmune hepatitis and its potential mechanism underlying AIH progression. METHODS: Plasma and intrahepatic sFGL2 levels, as well as Treg cells, were measured in both AIH patients and experimental autoimmune hepatitis (EAH) mice...
May 14, 2018: Journal of Gene Medicine
Julian Ramírez-Bello, Daniel Cadena-Sandoval, José Manuel Fragoso, Rosa Elda Barbosa-Cobos, Mario Adán Moreno-Eutímio, Miguel Ángel Saavedra-Salinas, Guillermo Valencia-Pacheco, Ricardo F López-Villanueva, Silvia Jiménez-Morales
BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention...
June 2018: Journal of Gene Medicine
Thorsten Bergmann, Eric Ehrke-Schulz, Jian Gao, Maren Schiwon, Verena Schildgen, Stephan David, Oliver Schildgen, Anja Ehrhardt
BACKGROUND: Gene correction at specific target loci provides a powerful strategy for overcoming genetic diseases. In the present study, we aimed to use an in vitro model for canine hemophilia B containing a single point mutation in the catalytic domain of the canine coagulation factor IX (cFIX) gene. To correct the defective gene via homology-directed repair (HDR), we designed transcription-activator like effector nucleases and clustered regularly interspaced short palindromic repeats including Cas9 (CRISPR/Cas9) for introduction of double-strand breaks at the mutation site...
May 2018: Journal of Gene Medicine
Simone Gabner, Reinhard Ertl, Karsten Velde, Matthias Renner, Florien Jenner, Monika Egerbacher, Juraj Hlavaty
BACKGROUND: A combination of tissue engineering methods employing mesenchymal stem cells (MSCs) together with gene transfer takes advantage of innovative strategies and highlights a new approach for targeting osteoarthritis (OA) and other cartilage defects. Furthermore, the development of systems allowing tunable transgene expression as regulated by natural disease-induced substances is highly desirable. METHODS: Bone marrow-derived equine MSCs were transduced with a lentiviral vector expressing interleukin-1 receptor antagonist (IL-1Ra) gene under the control of an inducible nuclear factor-kappa B-responsive promoter and IL-1Ra production upon pro-inflammatory cytokine stimulation [tumor necrosis factor (TNF)α, interleukin (IL)-1β] was analysed...
May 2018: Journal of Gene Medicine
Olga E Bryzgunova, Maria Yu Konoshenko, Pavel P Laktionov
Insight into the aberrant expression of microRNAs (miRNAs) and the genes that they regulate during the progression of cancer in general and prostate cancer (PCa) in particular is one of the most important issues in current molecular biomedicine and allows for the discovery of therapeutic or diagnostic miRNA targets. The present study aimed to analyze the available data regarding the direct or indirect effects of miRNAs on the expression of the mRNAs involved in carcinogenesis and to enable updating and optimizing the selection of the corresponding targets...
May 2018: Journal of Gene Medicine
Binhai Ren, Que T La, Bronwyn A O'Brien, Najah T Nassif, Yi Tan, Dario Gerace, Rosetta Martiniello-Wilks, Fraser Torpy, Allison P Dane, Ian E Alexander, Ann M Simpson
BACKGROUND: Gene therapy is one treatment that may ultimately cure type 1 diabetes. We have previously shown that the introduction of furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes resulted in the reversal of diabetes and partial pancreatic transdifferentiation of liver cells. The present study investigated whether streptozotocin-diabetes could be reversed in FRG mice in which chimeric mouse-human livers can readily be established and, in addition, whether pancreatic transdifferentiation occurred in the engrafted human hepatocytes...
May 2018: Journal of Gene Medicine
Samantha L Ginn, Anais K Amaya, Ian E Alexander, Michael Edelstein, Mohammad R Abedi
To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries...
May 2018: Journal of Gene Medicine
Shuang Long, Na Zhao, Lan Ge, Guojian Wang, Xinze Ran, Junping Wang, Yongping Su, Tao Wang
BACKGROUND: The cellular and molecular mechanisms responsible for the age-associated delay of cutaneous wound healing are still not well understood. Previous studies have shown that miR-21 plays key roles during skin wound healing. We presumed that dysregulation of miR-21 may be involved in age-associated defects in wound healing and that miR-21 may be one potential therapeutic target by which to ameliorate wound defects in elderly subjects. METHODS: Circular full thickness excisional wounds were made on the dorsal skin of young (2-month-old) and aged (12-month-old) female mice...
April 15, 2018: Journal of Gene Medicine
Sachie Nakamura, Shin-Ichi Muramatsu, Naomi Takino, Mika Ito, Eriko F Jimbo, Kuniko Shimazaki, Tatsushi Onaka, Sumio Ohtsuki, Tetsuya Terasaki, Takanori Yamagata, Hitoshi Osaka
BACKGROUND: We generated an adeno-associated virus (AAV) vector in which the human SLC2A1 gene, encoding glucose transporter type 1 (GLUT1), was expressed under the human endogenous GLUT1 promoter (AAV-GLUT1). We examined whether AAV-GLUT1 administration could lead to functional improvement in GLUT1-deficient mice. METHODS: We extrapolated human endogenous GLUT1 promoter sequences from rat minimal Glut1 promoter sequences. We generated a tyrosine-mutant AAV9/3 vector in which human SLC2A1-myc-DDK was expressed under the human GLUT1 promoter (AAV-GLUT1)...
April 2018: Journal of Gene Medicine
Bong Jik Kim, Jin Hee Han, Hye-Rim Park, Min Young Kim, Ah Reum Kim, Seung-Ha Oh, Woong-Yang Park, Doo Yi Oh, Seungmin Lee, Byung Yoon Choi
BACKGROUND: The MYO6 gene, if altered, can cause nonsyndromic hearing loss (NSHL) either in an autosomal dominant (AD) (DFNA22) or recessive form. The present study identified MYO6 variants in the cohort of Korean AD NSHL families and investigated the audiological phenotypes of DFNA22 with respect to suggesting clinical guides for the counseling of DFNA22. METHODS: A retrospective cohort study was performed on 81 AD NSHL families in two hospitals. Among them, five families (SH21, SB60, SB247, SB290 and SB305) segregating with MYO6 variant were genetically and clinically assessed...
April 1, 2018: Journal of Gene Medicine
Monica Juneja, Uzma Shamim, Aditi Joshi, Aaradhna Mathur, Bharathram Uppili, Smitha Sairam, Sakshi Ambawat, Rashmi Dixit, Mohammed Faruq
BACKGROUND: Mutations in SLC39A14 cause a recessive disorder of manganese (Mn) metabolism that manifests as childhood onset progressive neurodegeneration characterized by parkinsonism and dystonia. METHODS: The present study genetically investigated a case of hypermanganesemia. We describe a family where an affected child with a history of progressive neurodegeneration showed symptoms of dystonia with increased levels of blood Mn and altered signal intensities in globus pallidus and dentate nucleus...
April 2018: Journal of Gene Medicine
Shing Cheng Tan
Colorectal cancer is a leading form of cancer in both males and females. Early detection of individuals at risk of colorectal cancer allows proper treatment and management of the disease to be implemented, which can potentially reduce the burden of colorectal cancer incidence, morbidity and mortality. In recent years, the role of genetic susceptibility factors in mediating predisposition to colorectal cancer has become more and more apparent. Identification of high-frequency, low-penetrance genetic polymorphisms associated with the cancer has therefore emerged as an important approach which can potentially aid prediction of colorectal cancer risk...
April 2018: Journal of Gene Medicine
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