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Non viral vectors

Joanna Bukowska, Trivia Frazier, Stanley Smith, Theodore Brown, Robert Bender, Michelle McCarthy, Xiying Wu, Bruce A Bunnell, Jeffrey M Gimble
PURPOSE OF REVIEW: This review explores how the relationships between bone marrow adipose tissue (BMAT) adipogenesis with advancing age, obesity, and/or bone diseases (osteopenia or osteoporosis) contribute to mechanisms underlying musculoskeletal pathophysiology. RECENT FINDINGS: Recent studies have re-defined adipose tissue as a dynamic, vital organ with functions extending beyond its historic identity restricted solely to that of an energy reservoir or sink. "State of the art" methodologies provide novel insights into the developmental origin, physiology, and function of different adipose tissue depots...
April 18, 2018: Current Osteoporosis Reports
Emanuele Sasso, Debora Latino, Guendalina Froechlich, Mariangela Succoio, Margherita Passariello, Claudia De Lorenzo, Alfredo Nicosia, Nicola Zambrano
Use of monoclonal antibodies is emerging as a highly promising and fast-developing scenario for innovative treatment of viral, autoimmune and tumour diseases. The search for diagnostic and therapeutic antibodies currently depends on in vitro screening approaches, such as phage and yeast display technologies. Antibody production still represents a critical step for preclinical and clinical evaluations. Accordingly, improving production of monoclonal antibodies represents an opportunity, to facilitate downstream target validations...
April 16, 2018: MAbs
B W Narladkar
Broadly, species of arthropods infesting livestock are grouped into flies (biting and non-biting), fleas, lice (biting and sucking), ticks (soft and hard), and mites (burrowing, non-burrowing, and follicular). Among which, biting and non-biting flies and ticks are the potent vectors for many bacterial, viral, rickettsial, and protozoan diseases. Vectors of livestock are having economic significance on three points (1) direct losses from their bite and annoyance, worries, and psychological disturbances produced during the act of biting and feeding, (2) diseases they transmit, and (3) expenditure incurred for their control...
February 2018: Veterinary World
Paul L Boyer, Steven J Smith, Xue Zhi Zhao, Kalyan Das, Kevin Gruber, Eddy Arnold, Terrence R Burke, Stephen H Hughes
We tested three compounds for their ability to inhibit the RNase H (RH) and polymerase activities of HIV-1 reverse transcriptase (RT). A high-resolution crystal structure (2.2 Å) of one of the compounds showed that it chelates the two magnesium ions at the RH active site; this prevents the RH active site from interacting with, and cleaving, the RNA strand of an RNA/DNA heteroduplex. The compounds were tested using a variety of substrates: All three compounds inhibited the polymerase-independent RH activity of HIV-1 RT...
April 11, 2018: Journal of Virology
Muhammad Farooq Rai, Christine Tn Pham
Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, current IA-injected drugs are rapidly cleared and do not significantly affect the course of joint disease. In this review, we highlight recent developments in IA therapy, with a special emphasis on current and emerging therapeutic carriers and their potential to deliver disease-modifying treatment modalities for arthritis...
April 3, 2018: Current Opinion in Pharmacology
Matthew W Grol, Brendan H Lee
Gene therapy refers to the use of viral and non-viral vectors to deliver nucleic acids to tissues of interest using direct (in vivo) or transduced cell-mediated (ex vivo) approaches. Over the past few decades, strategies have been adopted to express therapeutic transgenes at sites of injury to promote or facilitate repair of bone and cartilage. Targets of interest have typically included secreted proteins such as growth factors and anti-inflammatory mediators; however, work has also begun to focus intracellularly on signaling components, transcription factors and small, regulatory nucleic acids such as microRNAs (miRNAs)...
April 2, 2018: Current Opinion in Pharmacology
Qiang Guo, Jasper Fuk-Woo Chan, Vincent Kwok-Man Poon, Shipo Wu, Chris Chung-Sing Chan, Lihua Hou, Cyril Chik-Yan Yip, Changpeng Ren, Jian-Piao Cai, Mengsu Zhao, Anna Jinxia Zhang, Xiaohong Song, Kwok-Hung Chan, Busen Wang, Kin-Hang Kok, Yanbo Wen, Kwok-Yung Yuen, Wei Chen
Background: Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and non-vector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic as they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of two previously reported adenovirus-vectored ZIKV vaccines were performed using non-lethal animal models and/or non-epidemic ZIKV strain...
March 29, 2018: Journal of Infectious Diseases
Shuang Peng, Binglin Bie, Yangzesheng Sun, Min Liu, Hengjiang Cong, Wentao Zhou, Yucong Xia, Heng Tang, Hexiang Deng, Xiang Zhou
Effective transfection of genetic molecules such as DNA usually relies on vectors that can reversibly uptake and release these molecules, and protect them from digestion by nuclease. Non-viral vectors meeting these requirements are rare due to the lack of specific interactions with DNA. Here, we design a series of four isoreticular metal-organic frameworks (Ni-IRMOF-74-II to -V) with progressively tuned pore size from 2.2 to 4.2 nm to precisely include single-stranded DNA (ssDNA, 11-53 nt), and to achieve reversible interaction between MOFs and ssDNA...
April 3, 2018: Nature Communications
Christian Stutzer, Sabine A Richards, Mariette Ferreira, Samantha Baron, Christine Maritz-Olivier
Eukaryotic parasites and pathogens continue to cause some of the most detrimental and difficult to treat diseases (or disease states) in both humans and animals, while also continuously expanding into non-endemic countries. Combined with the ever growing number of reports on drug-resistance and the lack of effective treatment programs for many metazoan diseases, the impact that these organisms will have on quality of life remain a global challenge. Vaccination as an effective prophylactic treatment has been demonstrated for well over 200 years for bacterial and viral diseases...
2018: Frontiers in Cellular and Infection Microbiology
David P Walsh, Robert D Murphy, Angela Panarella, Rosanne Marie Raftery, Brenton Cavanagh, Jeremy Charles Simpson, Fergal J O'Brien, Andreas Heise, Sally-Ann Cryan
The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(L-lysine) polypeptide (star-PLL) with varying number and length of poly(L-Lysine) arms as potential non-viral gene delivery vectors for MSCs...
March 28, 2018: Molecular Pharmaceutics
Matthew T Aliota, Dawn M Dudley, Christina M Newman, James Weger-Lucarelli, Laurel M Stewart, Michelle R Koenig, Meghan E Breitbach, Andrea M Weiler, Matthew R Semler, Gabrielle L Barry, Katie R Zarbock, Amelia K Haj, Ryan V Moriarty, Mariel S Mohns, Emma L Mohr, Vanessa Venturi, Nancy Schultz-Darken, Eric Peterson, Wendy Newton, Michele L Schotzko, Heather A Simmons, Andres Mejia, Jennifer M Hayes, Saverio Capuano, Miles P Davenport, Thomas C Friedrich, Gregory D Ebel, Shelby L O'Connor, David H O'Connor
Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission, pathogenesis, immune evasion, and potential reservoir establishment. Within-host viral diversity in ZIKV infection is low, which makes it difficult to evaluate infection dynamics. To overcome this biological hurdle, we constructed a molecularly barcoded ZIKV. This virus stock consists of a "synthetic swarm" whose members are genetically identical except for a run of eight consecutive degenerate codons, which creates approximately 64,000 theoretical nucleotide combinations that all encode the same amino acids...
March 28, 2018: PLoS Pathogens
Hamidreza Hashemi, Alexandra-Larisa Condurat, Alexandra Stroh-Dege, Nadine Weiss, Carsten Geiss, Jill Pilet, Carles Cornet Bartolomé, Jean Rommelaere, Nathalie Salomé, Christiane Dinsart
Single nucleotide changes were introduced into the non-structural (NS) coding sequence of the H-1 parvovirus (PV) infectious molecular clone and the corresponding virus stocks produced, thereby generating H1-PM-I, H1-PM-II, H1-PM-III, and H1-DM. The effects of the mutations on viral fitness were analyzed. Because of the overlapping sequences of NS1 and NS2, the mutations affected either NS2 (H1-PM-II, -III) or both NS1 and NS2 proteins (H1-PM-I, H1-DM). Our results show key benefits of PM-I, PM-II, and DM mutations with regard to the fitness of the virus stocks produced...
March 27, 2018: Viruses
Julia N Khantakova, Alexander N Silkov, Valeriy P Tereshchenko, Elena V Gavrilova, Rinat A Maksyutov, Sergey V Sennikov
In vitro electroporation gene transfer was first performed in 1982. Today, this technology has become one of the major vehicles for non-viral transfection of cells. All non-viral transfections, such as calcium phosphate precipitation, lipofection, and magnetic transfection, have been shown to achieve a transfection efficiency of up to 70% in commonly used cell lines, but not in primary cells. Here we describe the use of electroporation to transfect primary mouse bone marrow-derived cells, such as macrophages (Mφ) and dendritic cells (DCs) with high efficiencies (45%-72%) and minimal cell death...
March 23, 2018: Cytokine
Marcos Alexandre Nobre Lemos, Sandra Fernanda Suarez Patiño, Thaissa Consoni Bernardino, Ana Sofia Coroadinha, Hugo Soares, Renato Mancini Astray, Carlos Augusto Pereira, Soraia Attie Calil Jorge
Viral hepatitis caused by the hepatitis C virus (HCV) affects millions of people worldwide. The non-structural protein 3 (NS3), one of the most conserved proteins in HCV, is the target of many therapeutic studies. The NS3 protease domain (NS3p) has a range of cytotoxic T lymphocyte (CTL) epitopes, and synthesizing the protein inside the cells is the most appropriate way to present it to the immune system. We developed a tool to study this kind of presentation, using two vectored particle (VP) systems, one based on the Semliki Forest virus (SFV) and the other on HCV pseudoparticles (HCVpp), both carrying the protease domain of the NS3 gene...
March 22, 2018: Journal of Biotechnology
Lin Wei, Di Zhang, Xuanfang Zheng, Xuyao Zeng, Youlin Zeng, Xinbo Shi, Xin Su, Lehui Xiao
Development of efficient non-viral gene delivery vector has aroused great attention in the past few decades. In this study, we reported a new gene delivery vector, positively charged fluorescent conjugated polymer nanoparticles (CPNPs), for efficient gene transfection and in-situ intracellular fluorescence imaging. The microscopic and spectroscopic characterizations demonstrated that these CPNPs possess decent fluorescence performance (e.g. with fluorescence quantum yield of 70.7±0.3%) and small size dimension of ~3...
2018: Nanotheranostics
Shuang Fu, Xiaodong Xu, Yu Ma, Shubiao Zhang, Shufen Zhang
Integrin αv β3 is restrictedly expressed on angiogenic blood vessels and tumor cells. It plays a key role in angiogenesis for tumor growth and metastasis. RGD peptide can specifically recognize the integrin αv β3 , which serve as targeted molecular for anti-angiogenesis strategies. Therefore, targeted delivery of therapeutics by RGD peptide based non-viral vectors to tumor vasculature and tumor cells is recognized as a promising approach for treating cancer. In this review, we illustrate the interaction between RGD peptide and integrin αv β3 from different perspectives...
March 22, 2018: Journal of Drug Targeting
Julian Clauß, Matthias Obenaus, Csaba Miskey, Zoltán Ivics, Zsuzsanna Izsvák, Wolfgang Uckert, Mario Bunse
Transposon-based vectors have entered clinical trials as an alternative to viral vectors for genetic engineering of T cells. However, transposon vectors require DNA transfection into T cells which we found to cause adverse effects. T cell viability was decreased in a dose-dependent manner and DNA-transfected T cells showed a delayed response upon T cell receptor (TCR) stimulation with regard to blast formation, proliferation and surface expression of CD25 and CD28. Gene expression analysis demonstrated a DNA-dependent induction of a type I interferon response and IFN-β upregulation...
March 21, 2018: Human Gene Therapy
Larissa Bueno Tofani, Lívia Vieira Depieri, Patrícia Mazureki Campos, Thalita Bachelli Riul, Kamilla Swiech Antonietto, Márcia Carvalho de Abreu Fantini, Maria Vitória Lopes Badra Bentley
PURPOSE: Vitiligo is a skin disease characterized by depigmentation and the presence of white patches that are associated with the loss of melanocytes. The most common explanation for the cause of this condition is that it is an autoimmune condition. TyRP-1 is involved in melanin pigment synthesis but can also function as a melanocyte differentiation antigen. This protein plays a role in the autoimmune destruction of melanocytes, which results in the depigmentation, characteristic of this disease...
March 20, 2018: Pharmaceutical Research
Qiaoxian Huang, Shengke Li, Yuan-Fu Ding, Hang Yin, Lian-Hui Wang, Ruibing Wang
Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied for gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has severely limited its clinical application. To resolve this dilemma, a supramolecular strategy was developed for the first time, in which PEI with large M.W. (branched, 25 kDa) that has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery was wrapped with macrocyclic cucurbit[7]uril (CB[7])...
March 20, 2018: Biomaterials Science
Ioannis N Mammas, Demetrios A Spandidos
According to Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School and Director of the Spinal Muscular Atrophy (SMA) Program at Boston Children's Hospital in Boston (MA, USA), the diagnosis of SMA type I is clinical and is based on detailed general physical and neurological examinations. SMA type I remains the most common genetic disease resulting in death in infancy and is really devastating for the child, the parents, as well as the medical professionals with the privilege of caring for patients with SMA and their parents...
April 2018: Experimental and Therapeutic Medicine
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