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Effect of genetically engineered

Sarah Aref, Katharine Bailey, Adele Fielding
Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis...
October 22, 2016: Viruses
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
J Suriya, S Bharathiraja, P Manivasagan, S-K Kim
Actinobacteria constitute rich sources of novel biocatalysts and novel natural products for medical and industrial utilization. Although actinobacteria are potential source of economically important enzymes, the isolation and culturing are somewhat tough because of its extreme habitats. But now-a-days, the rate of discovery of novel compounds producing actinomycetes from soil, freshwater, and marine ecosystem has increased much through the developed culturing and genetic engineering techniques. Actinobacteria are well-known source of their bioactive compounds and they are the promising source of broad range of industrially important enzymes...
2016: Advances in Food and Nutrition Research
Nasser K Yaghi, Jun Wei, Yuuri Hashimoto, Ling-Yuan Kong, Konrad Gabrusiewicz, Edjah K Nduom, Xiaoyang Ling, Neal Huang, Shouhao Zhou, Brittany C Parker Kerrigan, Jonathan M Levine, Virginia R Fajt, Gwendolyn Levine, Brian F Porter, Eric G Marcusson, Kiyoshi Tachikawa, Padmanabh Chivukula, David C Webb, Joseph E Payne, Amy B Heimberger
BACKGROUND: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. METHODS: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects...
October 8, 2016: Neuro-oncology
Qingsong Liu, Eric Hallerman, Yufa Peng, Yunhe Li
Rice and maize are important cereal crops that serve as staple foods, feed, and industrial material in China. Multiple factors constrain the production of both crops, among which insect pests are an important one. Lepidopteran pests cause enormous yield losses for the crops annually. In order to control these pests, China plays an active role in development and application of genetic engineering (GE) to crops, and dozens of GE rice and GE maize lines expressing insecticidal proteins from the soil bacterium Bacillus thuringiensis (Bt) have been developed...
October 18, 2016: International Journal of Molecular Sciences
Gaia Pigna, Taniya Dhillon, Elizabeth M Dlugosz, Joshua S Yuan, Connor Gorman, Piero Morandini, Scott C Lenaghan, C Neal Stewart
Arundo donax L. is a promising biofuel feedstock in the Mediterranean region. Despite considerable interest in its genetic improvement, Arundo tissue culture and transformation remains arduous. We developed methodologies for cell- and tissue culture and genetic engineering in Arundo. A media screen was conducted, and a suspension culture was established using callus induced from stem axillary bud explants. DBAP medium, containing 9 μM 2,4-D and 4.4 μM BAP, was found to be the most effective medium among those tested for inducing cell suspension cultures, which resulted in a 5-fold increase in tissue mass over 14 days...
October 20, 2016: Biotechnology Journal
Hye-Hyeon Byeon, Seung-Woo Lee, Eun-Hee Lee, Woong Kim, Hyunjung Yi
Delicately assembled composites of semiconducting nanomaterials and biological materials provide an attractive interface for emerging applications, such as chemical/biological sensors, wearable health monitoring devices, and therapeutic agent releasing devices. The nanostructure of composites as a channel and a sensing material plays a critical role in the performance of field effect transistors (FETs). Therefore, it is highly desirable to prepare elaborate composite that can allow the fabrication of high performance FETs and also provide high sensitivity and selectivity in detecting specific chemical/biological targets...
October 20, 2016: Scientific Reports
Walter H Moos, Carl A Pinkert, Michael H Irwin, Douglas V Faller, Krishna Kodukula, Ioannis P Glavas, Kosta Steliou
Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population...
October 20, 2016: Drug Development Research
Shigeru Shibata, Kenichi Ishizawa, Shunya Uchida
The kidney has a central role in long-term control of blood pressure, and decreased kidney function is a common but difficult-to-treat cause of hypertension. Conversely, elevated blood pressure contributes to the progression of chronic kidney disease. Steroid hormone aldosterone and its receptor mineralocorticoid receptor (MR) contribute to hypertension by increasing renal salt reabsorption and promote kidney dysfunction through direct effects on renal parenchymal cells. Accumulating data indicate that various mechanisms affect aldosterone-MR signaling...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Atsuo Ogura
Reproductive engineering techniques are essential for assisted reproduction of animals and generation of genetically modified animals. They may also provide invaluable research models for understanding the mechanisms involved in the developmental and reproductive processes. At the RIKEN BioResource Center (BRC), I have sought to develop new reproductive engineering techniques, especially those related to cryopreservation, microinsemination (sperm injection), nuclear transfer, and generation of new stem cell lines and animals, hoping that they will support the present and future projects at BRC...
October 19, 2016: Experimental Animals
Chaudhari Archana Somabhai, Ruma Raghuvanshi, G Nareshkumar
AIMS: To assess protective efficacy of genetically modified Escherichia coli Nissle 1917 (EcN) on metabolic effects induced by chronic consumption of dietary fructose. MATERIALS AND METHODS: EcN was genetically modified with fructose dehydrogenase (fdh) gene for conversion of fructose to 5-keto-D-fructose and mannitol-2-dehydrogenase (mtlK) gene for conversion to mannitol, a prebiotic. Charles foster rats weighing 150-200 g were fed with 20% fructose in drinking water for two months...
2016: PloS One
Paulina J Paszkiewicz, Simon P Fräßle, Shivani Srivastava, Daniel Sommermeyer, Michael Hudecek, Ingo Drexler, Michel Sadelain, Lingfeng Liu, Michael C Jensen, Stanley R Riddell, Dirk H Busch
The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface...
October 17, 2016: Journal of Clinical Investigation
Shigeo Ohba, Joydeep Mukherjee, Tor-Christian Johannessen, Andrew Mancini, Tracy T Chow, Matthew Wood, Lindsey Jones, Tali Mazor, Roxanne E Marshall, Pavithra Viswanath, Kyle M Walsh, Arie Perry, Robert J A Bell, Joanna J Phillips, Joseph F Costello, Sabrina M Ronen, Russell O Pieper
Mutations in the isocitrate dehydrogenase gene IDH1 are common in lower-grade glioma where they result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation and gliomagenesis. IDH1 mutations also co-segregate with mutations in the ATRX gene and the TERT promoter, suggesting that IDH mutation may drive the creation or selection of telomere-stabilizing events as part of immortalization/transformation process. To determine if and how this may occur, we investigated the phenotype of pRb/p53-deficient human astrocytes engineered with IDH1 wild-type (WT) or R132H mutant (IDH1mut) genes as they progressed through their lifespan...
October 6, 2016: Cancer Research
Kara W Moyes, Nicole Ap Lieberman, Shannon A Kreuser, Harrison Chinn, Conrad Winter, Gail Deutsch, Virginia Hoglund, Reid Watson, Courtney A Crane
In spite of their successes against hematologic malignancies, immunotherapeutic interventions for the treatment of patients with glioblastoma (GBM) have thus far been unsuccessful. This is in part due to the presence of a tumor microenvironment that fosters neoplastic growth and protects the tumor from destruction by the immune system. We have developed a novel genetically engineered macrophage-based platform with the potential to minimize the effects of the suppressive tumor microenvironment and improve innate and adaptive anti-tumor immune responses...
October 19, 2016: Human Gene Therapy
Carlos Vera, Andrés Córdova, Carla Aburto, Cecilia Guerrero, Sebastián Suárez, Andrés Illanes
Lactose-derived non-digestible oligosaccharides are prominent components of functional foods. Among them, galacto-oligosaccharides (GOS) outstand for being prebiotics whose health-promoting effects are supported on strong scientific evidences, having unique properties as substitutes of human milk oligosaccharides in formulas for newborns and infants. GOS are currently produced enzymatically in a kinetically-controlled reaction of lactose transgalactosylation catalyzed by β-galactosidases from different microbial strains...
December 2016: World Journal of Microbiology & Biotechnology
Xiaolong Wang, Bei Cai, Jiankui Zhou, Haijing Zhu, Yiyuan Niu, Baohua Ma, Honghao Yu, Anmin Lei, Hailong Yan, Qiaoyan Shen, Lei Shi, Xiaoe Zhao, Jinlian Hua, Xingxu Huang, Lei Qu, Yulin Chen
Precision genetic engineering accelerates the genetic improvement of livestock for agriculture and biomedicine. We have recently reported our success in producing gene-modified goats using the CRISPR/Cas9 system through microinjection of Cas9 mRNA and sgRNAs targeting the MSTN and FGF5 genes in goat embryos. By investigating the influence of gene modification on the phenotypes of Cas9-mediated goats, we herein demonstrate that the utility of this approach involving the disruption of FGF5 results in increased number of second hair follicles and enhanced fiber length in Cas9-mediated goats, suggesting more cashmere will be produced...
2016: PloS One
Logan Horne, Frank R Avilucea, Huifeng Jin, Jared J Barrott, Kyllie Smith-Fry, Yanliang Wang, Bang H Hoang, Kevin B Jones
Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5) in osteosarcoma (OS) tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5), which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained...
October 2016: Translational Oncology
Alicia M Waters, Laura L Stafman, Evan F Garner, Smitha Mruthyunjayappa, Jerry E Stewart, Gregory K Friedman, Jennifer M Coleman, James M Markert, G Yancey Gillespie, Elizabeth A Beierle
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134...
October 2016: Translational Oncology
Khawaja Muhammad Imran Bashir, Man-Gi Cho
Antibiotics are routinely used in microalgae culture screening, stock culture maintenance, and genetic transformation. By studying the effect of antibiotics on microalgae growth, we can estimate the least value to inhibit growth of undesired pathogens in algal culture. We studied the effect of kanamycin and tetracycline on the growth and photosynthetic activity of two chlorophyte microalgae, Dictyosphaerium pulchellum and Micractinium pusillum. We measured CFU mL(-1) on agar plates, optical density, fluorescence yields, and photosynthetic inhibition...
2016: BioMed Research International
Suvi T Häkkinen, Elisabeth Moyano, Rosa M Cusidó, Kirsi-Marja Oksman-Caldentey
Plants remain a major source of new drugs, leads and fine chemicals. Cell cultures deriving from plants offer a fascinating tool to study plant metabolic pathways and offer large scale production systems for valuable compounds - commercial examples include compounds such as paclitaxel. The major constraint with undifferentiated cell cultures is that they are generally considered to be genetically unstable and cultured cells tend to produce low yields of secondary metabolites especially over time. Hairy roots, a tumor tissue caused by infection of Agrobacterium rhizogenes is a relevant alternative for plant secondary metabolite production for being fast growing, able to grow without phytohormones, and displaying higher stability than undifferentiated cells...
2016: Frontiers in Plant Science
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