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Preview: MedWorm: Gene Therapy

MedWorm: Gene Therapy provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Gene Therapy category.

Last Build Date: Tue, 29 Mar 2016 16:21:59 +0100


Engineering of measles virus to target cancer cells, an attempt

Tue, 29 Mar 2016 09:23:36 +0100

Background: Regardless of general perception as potentially dangerous pathogens, viruses have been exploited and used as vaccine agents or as carriers for gene therapy. Similar positive effects have been observed in case of cancer patients getting infected with viruses, where infection has resulted in temporary tumor regression. Hence, the development of a recombinant virus that selectively infects and kills cancer cells can be a promising anti-cancer tool in near future. Here we made an attempt to generate an oncolytic virus using Measles viral genome (Edmonston strain) backbone and to further arm this recombinant virus with non viral genes of known anti-proliferative activity to enhance its antitumor activity. (Source: International Journal of Infectious Diseases)

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Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

Mon, 28 Mar 2016 21:37:01 +0100

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In additio...

Mp30-04 herpes simplex virus (hsv) vector-mediated gene delivery of poreless trpv1 channels or protein phosphate 1α (pp1α) reduces bladder overactivity and nociception in rat model of cystitis induced by hydrogen peroxide

Mon, 28 Mar 2016 19:24:06 +0100

It has been reported that increased afferent excitability is an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) and that transient receptor potential vanilloid-1 (TRPV1) receptors greatly contribute to afferent sensitization. Animals with hydrogen peroxide (HP)-induced cystitis have recently been introduced as a model that mimics pathologic features of chronic inflammatory bladder condition. Therefore, we investigated the effect of gene therapy with HSV vectors encoding poreless TRPV1 or PP1α (negative TRPV1 modulator) in rats with HP-induced cystitis. (Source: The Journal of Urology)

Mp83-12 in vitro effects of interferon alpha in bladder cancer: immune checkpoint expression and microrna and mrna genomic profiling

Mon, 28 Mar 2016 19:24:03 +0100

Current intravesical treatments for non-muscle invasive bladder cancer are suboptimal, as demonstrated by significant rates of recurrence and progression. Interferon-alpha (IFNa) might be more effective in the setting of adenoviral vector mediated IFNa gene therapy (already in clinical trials) or immune checkpoint blockade. Here we characterize bladder cancer cell lines expression of immune checkpoint PD-L1, micro-RNA (miR), and mRNA expression profiles after treatment with IFNa. (Source: The Journal of Urology)

Vector serotype screening for use in ovine perinatal lung gene therapy

Sun, 27 Mar 2016 22:00:00 +0100

Successful in utero or perinatal gene therapy for congenital lung diseases, such as cystic fibrosis and surfactant protein deficiency, requires identifying clinically relevant viral vectors that efficiently transduce airway epithelial cells. The purpose of the current preclinical large animal study was to evaluate lung epithelium transduction of adeno-associated viral (AAV) vector serotypes following intratracheal delivery. (Source: Journal of Pediatric Surgery)

Atomic force microscopy as a tool to study the adsorption of DNA onto lipid interfaces

Sat, 26 Mar 2016 01:07:05 +0100

ABSTRACT The Atomic Force Microscopy (AFM) technique appears as a central tool for the characterization of DNA adsorption onto lipid interfaces. Regardless of the huge number of surveys devoted to this issue, there are still fascinating phenomena in this field that have not been explored in detail by AFM. For instance, adsorption of DNA onto like‐charged lipid surfaces mediated by cations is still not fully understood even though it is gaining popularity nowadays in gene therapy and nanotechnology. Studies related to the complexation of DNA with anionic lipids as a non‐viral gene delivery vehicle as well as the formation of self‐assembled nanoscale DNA constructs (DNA origami) are two of the most attractive systems. Unfortunately, molecular mechanisms underlying the adsorption of DNA...

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Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo.

Fri, 25 Mar 2016 17:35:02 +0100

This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment. PMID: 27004535 [PubMed - as supplied by publisher] (Source: Oncology Reports)

Integrated analysis of long non-coding RNAs in human colorectal cancer.

Fri, 25 Mar 2016 17:33:04 +0100

Authors: Chen X, Liu B, Yang R, Guo Y, Li F, Wang L, Hu H Abstract Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in tumors. However, the genome-wide expression and roles of lncRNAs in colorectal cancer (CRC) remain unknown. Here, we systematically examined the global gene expressions in primary and synchronous liver metastases CRC tissue, in which thousands of aberrantly expressed lncRNAs were characterized. Co-expression analysis revealed that some lncRNAs correlated to their neighboring mRNAs in expression levels, whereas others formed networks with protein-coding genes in trans. We observed H3K4me3 was enriched at expressed lncRNA transcription start sites (TSSs) and correlated to dysregulated lncRNAs. Furthermore, we identified primary and metastas...

IVIG in autoimmune disease – Potential next generation biologics

Thu, 24 Mar 2016 23:00:00 +0100

Publication date: Available online 25 March 2016 Source:Autoimmunity Reviews Author(s): Adrian W. Zuercher, Rolf Spirig, Adriana Baz Morelli, Fabian Käsermann Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms releva...

Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells

Thu, 24 Mar 2016 23:00:00 +0100

To study whether efficient transduction and subsequent elimination of fibroid tumor-initiating stem cells during debulking of tumor cells will aid in completely eradicating the tumor as well as decreasing the likelihood of recurrence. (Source: Fertility and Sterility)

Silencing of hypoxia inducible factor-1α by RNA interference inhibits growth of SK-NEP-1 Wilms tumor cells in vitro, and suppresses tumorigenesis and angiogenesis in vivo.

Thu, 24 Mar 2016 23:00:00 +0100

This article is protected by copyright. All rights reserved. PMID: 27015631 [PubMed - as supplied by publisher] (Source: Clinical and Experimental Pharmacology and Physiology)

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Effect of rAAV2-hTGFβ1 Gene Transfer on Matrix Synthesis in an In Vivo Rabbit Disk Degeneration Model

Thu, 24 Mar 2016 20:34:54 +0100

Study Design: In vivo gene transfer for disk regeneration. Objective: To evaluate the efficiency and effect of human transforming growth factor β1 (hTGFβ1) gene transfer mediated by adeno-associated virus (AAV) in a rabbit disk degeneration model induced by fibronectin fragment (Fn-f). Summary of Background Data: Gene therapy for disk degeneration has been reported to be effective. Nevertheless, few investigations have targeted the degenerative nucleus pulposus (NP) cells in vivo. Fn-f-induced degeneration has been previously verified to be a useful model for the study of disk degeneration at the molecular level. AAV vector is well suited for gene transfer in the disk for its lower immunogenicity and higher safety. Materials and Methods: The early dedifferentiated NP cells were transf...

Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread

Wed, 23 Mar 2016 23:00:00 +0100

Authors: T Shibata, H Uchida, T Shiroyama, Y Okubo, T Suzuki, H Ikeda, M Yamaguchi, Y Miyagawa, T Fukuhara, J B Cohen, J C Glorioso, T Watabe, H Hamada & H Tahara (Source: Gene Therapy)

Axonal transport of AAV9 in nonhuman primate brain

Wed, 23 Mar 2016 23:00:00 +0100

Authors: F Green, L Samaranch, H S Zhang, A Manning-Bog, K Meyer, J Forsayeth & K S Bankiewicz (Source: Gene Therapy)

Effects of transgene expression level per cell in mice livers on induction of transgene-specific immune responses after hydrodynamic gene transfer

Wed, 23 Mar 2016 23:00:00 +0100

Authors: Y Yin, Y Takahashi, A Hamana, M Nishikawa & Y Takakura (Source: Gene Therapy)

Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease

Wed, 23 Mar 2016 23:00:00 +0100

Authors: L Y Teos, C-Y Zheng, X Liu, W D Swaim, C M Goldsmith, A P Cotrim, B J Baum & I S Ambudkar (Source: Gene Therapy)

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The Value Game

Wed, 23 Mar 2016 17:05:01 +0100

As the attitudes of payors change, pharma companies will need to up their game when it comes to explaining the value they offer. Gearing their sales efforts towards convincing doctors of the need to write a prescription is no longer enough for firms which need to see the maximum return on their expensive products. “That center of gravity is shifting away from physicians to payors,” explains Peter Hoang, Senior Vice President, Business Development & Strategy at Bellicum Pharmaceuticals. “Price compression and margin compression are going to make heavy R&D investment much more challenging.” Gravity shift Something has to change. Hoang, who will be speaking at eyeforpharma Philadelphia 2016 in May, sees that pharma has to strike a balance between selling and educating. Before ...

Construction and characterization of gelonin and saporin plasmids for toxic gene-based cancer therapy.

Tue, 22 Mar 2016 23:00:00 +0100

Authors: Min KA, He H, Yang VC, Shin MC Abstract Toxic gene therapy (or suicidal gene therapy) is gaining enormous interest, specifically for the treatment of cancer. The success of this therapy lies in several crucial factors, including the potency of gene products to kill the transfected tumor cells and the transfection ability of the transfection vehicles. To address the potency problem, in the present study, we engineered two separate mammalian transfection plasmids (pSAP and pGEL) containing genes encoding ribosome inactivating proteins (RIPs), gelonin and saporin. After the successful preparation and amplification of the plasmids, they were tested on various cancer cell lines (HeLa, U87, 9L, and MDA-MB-435) and a noncancerous cell line (293 HEK) using polyethyleneimine (PEI) ...

Improved osteogenic vector for non-viral gene therapy.

Tue, 22 Mar 2016 20:40:02 +0100

Authors: Hacobian AR, Posa-Markaryan K, Sperger S, Stainer M, Hercher D, Feichtinger GA, Schuh CM, Redl H Abstract Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2) gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp). T...

UC San Diego Health joins National Clinical Trial on hemophilia B gene therapy

Tue, 22 Mar 2016 04:00:00 +0100

(University of California - San Diego) The Hemophilia and Thrombosis Treatment Center at UC San Diego Health has joined a nationwide clinical trial testing a potential gene therapy that may one day provide a better and long-lasting treatment for people with hemophilia B. (Source: EurekAlert! - Medicine and Health)

A discussion on cell therapy in Manchester

Mon, 21 Mar 2016 23:00:00 +0100

Publication date: Available online 21 March 2016 Source:Stem Cell Research Author(s): Giulio Cossu, Roberto Buccione, Michele De Luca An EMBO conference on cell therapy and its clinical applications It might come as a surprise to many, that stem cell transplantation is actually an established, life saving therapy for certain diseases affecting the haematological system and stratified epithelia. This is made possible by the chemical (chemotherapy) or physical (radiation) ablation of the affected bone marrow or surgical removal of diseased epithelia. The elimination of affected tissues thus makes “room” for donor cells, which consequently engraft with high yields, effectively replacing the diseased tissue with a healthy one. This is, at the state of the art, clearly an impossible ta...

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Gene therapy grows up (and moves out of the house)

Mon, 21 Mar 2016 00:00:00 +0100

(Source: Human Molecular Genetics)

Advances in treatment of achondroplasia and osteoarthritis

Mon, 21 Mar 2016 00:00:00 +0100

Achondroplasia (ACH) is the prototype and most common of the human chondrodysplasias. It results from gain-of-function mutations that exaggerate the signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor tyrosine kinase that negatively regulates growth plate activity and linear bone growth. Several approaches to reduce FGFR3 signaling by blocking receptor activation or inhibiting downstream signals have been proposed. Five show promise in preclinical mouse studies. Two candidate therapies target the extracellular domain of FGFR3. The first is a decoy receptor that competes for activating ligands. The second is a synthetic blocking peptide that prevents ligands from binding and activating FGFR3. Two established drugs, statins and meclozine, improve growth of ACH mice. ...

Progress and prospects of gene therapy clinical trials for the muscular dystrophies

Mon, 21 Mar 2016 00:00:00 +0100

Clinical trials represent a critical avenue for new treatment development, where early phases (I, I/II) are designed to test safety and effectiveness of new therapeutics or diagnostic indicators. A number of recent advances have spurred renewed optimism toward initiating clinical trials and developing refined therapies for the muscular dystrophies (MD's) and other myogenic disorders. MD's encompass a heterogeneous group of degenerative disorders often characterized by progressive muscle weakness and fragility. Many of these diseases result from mutations in genes encoding proteins of the dystrophin–glycoprotein complex (DGC). The most common and severe form among children is Duchenne muscular dystrophy, caused by mutations in the dystrophin gene, with an average life expectancy aroun...

Progress toward improved therapies for inborn errors of metabolism

Mon, 21 Mar 2016 00:00:00 +0100

Because of their prevalence, severity and lack of effective treatments, inborn errors of metabolism need novel and more effective therapeutic approaches. The opportunity for an early treatment coming from expanded newborn screening has made this need even more urgent. To meet this demand, a growing number of novel treatments are entering in the phase of clinical development. Strategies to overcome the detrimental consequences of the enzyme deficiencies responsible for inborn errors of metabolism have been focused on multiple fronts at the levels of the gene, RNA, protein and whole cell. These strategies have been accomplished using a wide spectrum of approaches ranging from small molecules to enzyme replacement therapy, cell and gene therapy. The applications of new technologies in the fie...

Adeno-associated viral vectors for the treatment of hemophilia

Mon, 21 Mar 2016 00:00:00 +0100

Gene transfer studies for the treatment of hemophilia began more than two decades ago. A large body of pre-clinical work evaluated a variety of vectors and target tissues, but by the start of the new millennium it became evident that adeno-associated viral (AAV)-mediated gene transfer to the liver held great promise as a therapeutic tool. The transition to the clinical arena uncovered a number of unforeseen challenges, mainly in the form of a human-specific immune response against the vector that poses a significant limitation in the application of this technology. While the full nature of this response has not been elucidated, long-term expression of therapeutic levels of factor IX is already a reality for a small number of patients. Extending this success to a greater number of hemophili...

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Progress and challenges in viral vector manufacturing

Mon, 21 Mar 2016 00:00:00 +0100

Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include c...

Gene therapy for lysosomal storage disorders: a good start

Mon, 21 Mar 2016 00:00:00 +0100

Lysosomal storage disorders (LSDs) are a heterogeneous group of inherited diseases with a collective frequency of ~1 in 7000 births, resulting from the deficiency in one or more enzymes or transporters that normally reside within the lysosomes. Pathology results from the progressive accumulation of uncleaved lipids, glycoproteins and/or glycosaminoglycans in the lysosomes and secondary damages that affect the brain, viscera, bones and connective tissues. Most treatment modalities developed for LSD, including gene therapy (GT), are based on the lysosome-specific cross-correction mechanism, by which close proximity of normal cells leads to the correction of the biochemical consequences of enzymatic deficiency within the neighboring cells. Here, GT efforts addressing these disorders are revie...

Multifunctional pDNA‐Conjugated Polycationic Au Nanorod‐Coated Fe3O4 Hierarchical Nanocomposites for Trimodal Imaging and Combined Photothermal/Gene Therapy

Mon, 21 Mar 2016 00:00:00 +0100

It is very desirable to design multifunctional nanocomposites for theranostic applications via flexible strategies. The synthesis of one new multifunctional polycationic Au nanorod (NR)‐coated Fe3O4 nanosphere (NS) hierarchical nanocomposite (Au@pDM/Fe3O4) based on the ternary assemblies of negatively charged Fe3O4 cores (Fe3O4‐PDA), polycation‐modified Au nanorods (Au NR‐pDM), and polycations is proposed. For such nanocomposites, the combined near‐infrared absorbance properties of Fe3O4‐PDA and Au NR‐pDM are applied to photoacoustic imaging and photothermal therapy. Besides, Fe3O4 and Au NR components allow the nanocomposites to serve as MRI and CT contrast agents. The prepared positively charged Au@pDM/Fe3O4 also can complex plasmid DNA into pDNA/Au@pDM/Fe3O4 and efficientl...

Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

Sun, 20 Mar 2016 23:00:00 +0100

Authors: Yu-Wai-Man P Abstract Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID: 27002113 [PubMed - as supplied by publisher] (Source...

Invossa™(Tissuegene-C) in patients with osteoarthritis: A phase III trial

Sun, 20 Mar 2016 18:07:31 +0100

Purpose: Invossa™ (TissueGene-C) is a cell and gene therapy for osteoarthritis that contains non-transformed and transduced chondrocytes by the ratio of 3:1. The transduced cell employs ex-vivo gene delivery via a retrovirally transduced chondrocytes that overexpress transforming growth factor-β1 (TGF-β1). (Source: Osteoarthritis and Cartilage)

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Emerging preclinical pharmacological targets for Parkinson's disease.

Sat, 19 Mar 2016 17:51:03 +0100

Authors: More SV, Choi DK Abstract Parkinson's disease (PD) is a progressive neurological condition caused by the degeneration of dopaminergic neurons in the basal ganglia. It is the most prevalent form of Parkinsonism, categorized by cardinal features such as bradykinesia, rigidity, tremors, and postural instability. Due to the multicentric pathology of PD involving inflammation, oxidative stress, excitotoxicity, apoptosis, and protein aggregation, it has become difficult to pin-point a single therapeutic target and evaluate its potential application. Currently available drugs for treating PD provide only symptomatic relief and do not decrease or avert disease progression resulting in poor patient satisfaction and compliance. Significant amount of understanding concerning the path...

Modification of the hTERT promoter by heat shock elements enhances the efficiency and specificity of cancer targeted gene therapy.

Fri, 18 Mar 2016 10:42:02 +0100

CONCLUSIONS: The hTERT promoter is a potentially powerful tumour-specific promoter and gene therapy tool for cancer treatment. Incorporating heat-inducible therapeutic elements (8HSEs) into the hTERT promoter may enhance the efficiency and specificity of cancer targeting gene therapy under hyperthermic clinical conditions. PMID: 26981638 [PubMed - as supplied by publisher] (Source: International Journal of Hyperthermia)

The developing role of pharmacogenetics in psychiatry.

Fri, 18 Mar 2016 04:28:02 +0100

Authors: Touw DJ Abstract A great interindividual variability exists in biological response to drugs. This variability is partly attributable to pharmacodynamic factors (drug - receptor interactions) and partly to pharmacokinetic factors. Drugs can be eliminated from the body by renal clearance, metabolism or both. Although every tissue has some ability to metabolise xenobiotics like drugs, the liver is the principal organ of biotransformation. Major metabolising enzymes are the cytochrome-P450 mono-oxygenases, epoxide hydrolase, glucuronosyl-transferase, acetyl-transferase, sulfo-transferase and xanthine oxidase. Some of these enzymes display in a subset of subjects a 'normal' activity and in another subset of subjects a reduced or a greatly increased activity. This altered activi...

Coping with genetic burden.

Fri, 18 Mar 2016 04:28:02 +0100

Authors: Tibben A Abstract An increasing number of neurodegenerative diseases have been defined at the molecular level in recent years, making it possible to determine precisely the genotype before the onset of symptoms. Pre-symptomatic testing programs are available for Huntington disease (HD), hereditary cerebral haemorrhage with amyloid-Dutch type, inherited cerebral ataxia, myotonic dystrophy, and Alzheimer disease. Although treatment options such as gene therapy have no widespread application until now, and much has to be developed, the use of predictive DNA-diagnostics has become a clinical application for a number of hereditary diseases. For psychiatric disorders such as schizophrenia or bipolar disorders, there are indications for localisation of the genetic factors, but cl...

Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells

Fri, 18 Mar 2016 00:00:00 +0100

Authors: X Sun, C Xu, S-C Tang, J Wang, H Wang, P Wang, N Du, S Qin, G Li, S Xu, Z Tao, Dapeng Liu & H Ren (Source: Cancer Gene Therapy)

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Precise and efficient siRNA design: a key point in competent gene silencing

Fri, 18 Mar 2016 00:00:00 +0100

Authors: E Fakhr, F Zare & L Teimoori-Toolabi (Source: Cancer Gene Therapy)

Adenovirus-directed expression of TIPE2 suppresses gastric cancer growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling

Fri, 18 Mar 2016 00:00:00 +0100

Adenovirus-directed expression of TIPE2 suppresses gastric cancer growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling Cancer Gene Therapy advance online publication, March 18 2016. doi:10.1038/cgt.2016.6 Authors: Y Zhu, M Tao, J Wu, Y Meng, C Xu, Y Tian, X Zhou, J Xiang, H Zhang & Y Xie (Source: Cancer Gene Therapy)

Immunogenic cell death by oncolytic herpes simplex virus type 1 in squamous cell carcinoma cells

Fri, 18 Mar 2016 00:00:00 +0100

Authors: A Takasu, A Masui, M Hamada, T Imai, S Iwai & Y Yura (Source: Cancer Gene Therapy)

Genetic Testing for Eye Diseases: A Comprehensive Guide and Review of Ocular Genetic Manifestations from Anterior Segment Malformation to Retinal Dystrophy

Fri, 18 Mar 2016 00:00:00 +0100

Abstract Genetic eye diseases are a heterogeneous group that collectively involve every facet of the eye, ocular adnexa and visual system. An individual condition within this group may be rare or common, have an isolated finding or be part of a syndrome, may severely threaten survivability, significantly affect vision or may have no bearing on visual morbidity. There have been treatment successes and safety reports in clinical trials involving vector-based ocular gene therapies, and there are currently a significant number of loci and genes known to contribute to human ocular disease, many of which have been recently discovered due to recent advances in the field of molecular genetics. In addition to obtaining a medical history and performing a comprehensive ocular exam, acquiring...

Salmeterol enhances the cardiac response to gene therapy in Pompe disease

Fri, 18 Mar 2016 00:00:00 +0100

In this study we have evaluated 4 new drugs in GAA knockout (KO) mice in combination with an adeno-associated virus (AAV) vector encoding human GAA, 3 alternative β2 agonists and dehydroepiandrosterone (DHEA). Mice were injected with AAV2/9-CBhGAA (1E+11 vector particles) at a dose previously found to be partially effective at clearing glycogen storage from the heart. Heart GAA activity was significantly increased by either salmeterol (p <0.01) or DHEA (p <0.05), in comparison with untreated mice. Furthermore, glycogen content was reduced in the heart by treatment with DHEA (p >0.001), salmeterol (p <0.05), formoterol (p <0.01), or clenbuterol (p <0.01) in combination with the AAV vector, in comparison with untreated GAA-KO mice. Wirehang testing ...

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Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma

Fri, 18 Mar 2016 00:00:00 +0100

Conclusion: Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. (Source: Reproductive Sciences)

Postepy Hig Med Dosw 2016; 70:200-209 "Liposomes as non-viral carriers for genetic drugs"

Thu, 17 Mar 2016 15:20:56 +0100

Methods in cancer therapy particularly in recent years, are rapidly changing, due to the need of design of new, more effective therapeutic strategies. Very promising approach to treatment of the neoplastic diseases is antisense gene therapy. Due to the low toxicity of treatment and eliminating not only the symptoms but also the molecular causes of the disease it may represent a breakthrough in cancer therapies. Delivery of a therapeutic DNA or RNA oligonucleotides to the target cells in vivo requires suitable carrier system. Non-viral drug carriers are increasingly used in new systems of targeted gene therapy. This review presents new generation of non-viral carriers, and is focused on immunoliposomes finding potential application in targeted gene therapy. (Source: Postepy higieny i medycy...

Angiotensin II increases gene expression after selective intra-arterial adenovirus delivery in a rabbit model assessed using in vivo SSTR2-based reporter imaging

Thu, 17 Mar 2016 00:00:00 +0100

Conclusions Angiotensin II improves in vivo gene expression by adenovirus upon intra-arterial delivery and thus may improve gene therapy efficacy. In vivo SSTR2-based reporter imaging can be used to compare methodologies for improving gene expression. (Source: EJNMMI Research)

β1-Na+,K+-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury

Thu, 17 Mar 2016 00:00:00 +0100

β1-Na+,K+-ATPase gene therapy upregulates tight junctions to rescue lipopolysaccharide-induced acute lung injury Gene Therapy advance online publication, March 17 2016. doi:10.1038/gt.2016.19 Authors: X Lin, M Barravecchia, P Kothari, J L Young & D A Dean (Source: Gene Therapy)

Systemic injection of AAV9 carrying a periostin promoter targets gene expression to a myofibroblast-like lineage in mouse hearts after reperfused myocardial infarction

Thu, 17 Mar 2016 00:00:00 +0100

Authors: B A Piras, Y Tian, Y Xu, N A Thomas, D M O'Connor & B A French (Source: Gene Therapy)

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Opposing effects of Sca-1+ cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse

Thu, 17 Mar 2016 00:00:00 +0100

Opposing effects of Sca-1+ cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse Gene Therapy advance online publication, March 17 2016. doi:10.1038/gt.2016.21 Authors: K-H W Lau, S-T Chen, X Wang, S Mohan, J E Wergedal, C Kesavan, A K Srivastava, D S Gridley & S L Hall (Source: Gene Therapy)

TCR-engineered T cells to treat tumors: Seeing but not touching?

Wed, 16 Mar 2016 23:00:00 +0100

Authors: Debets R, Donnadieu E, Chouaib S, Coukos G Abstract Adoptive transfer of T cells gene-engineered with T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs that demonstrate antigen-selective responses that are restricted to tumor cells and, at the same time, include strategies that restore or enhance the entry, migration and local accumulation of T cells in tumor tissues. Here, we present the current standing of TCR-engineered T cell therapy, discuss and propose procedures to select TCRs as well as strategies to sensitize the tumor to T cell trafficking, and provide a rationale for combination therapies with TCR-...

Synthetic Biology—Toward Therapeutic Solutions

Wed, 16 Mar 2016 00:00:00 +0100

Publication date: 27 February 2016 Source:Journal of Molecular Biology, Volume 428, Issue 5, Part B Author(s): Viktor Haellman, Martin Fussenegger Higher multicellular organisms have evolved sophisticated intracellular and intercellular biological networks that enable cell growth and survival to fulfill an organism's needs. Although such networks allow the assembly of complex tissues and even provide healing and protective capabilities, malfunctioning cells can have severe consequences for an organism's survival. In humans, such events can result in severe disorders and diseases, including metabolic and immunological disorders, as well as cancer. Dominating the therapeutic frontier for these potentially lethal disorders, cell and gene therapies aim to relieve or eliminate patient suffe...

Fetal Gene Therapy for Ornithine Transcarbamylase Deficiency by Intrahepatic Plasmid DNA-Micro-bubble Injection Combined with Hepatic Ultrasound Insonation

Wed, 16 Mar 2016 00:00:00 +0100

We evaluated the therapeutic efficacy of hepatic transfection of plasmid DNA using micro-bubbles and ultrasound insonation for fetal correction of ornithine transcarbamylase (OTC) deficiency in mice. Twenty-three sparse-fur heterozygous pregnant mice (day 16 of gestation) were divided into three groups: injection of plasmid-DNA micro-bubble mixture into fetal liver with ultrasound insonation (Tr, n = 11); control group 1 (C1), injection of plasmid-DNA micro-bubble mixture into fetal liver with no insonation (n = 5); and control group 2 (C2), injection of saline–micro-bubble mixture into fetal liver with ultrasound insonation (n = 7). (Source: Ultrasound in Medicine and Biology)

Correction of Mutant p63 in EEC Syndrome Using siRNA Mediated Allele‐Specific Silencing Restores Defective Stem Cell Function

Wed, 16 Mar 2016 00:00:00 +0100

This study demonstrates the phenotypic correction of mutant stem cells (OMESCs) in EEC syndrome by means of siRNA mediated AS silencing with restoration of function. The application of siRNA, alone or in combination with cell‐based therapies, offers a therapeutic strategy for corneal blindness in EEC syndrome. Stem Cells 2016; 00:000—000 (Source: Stem Cells)

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Pay-for-performance pricing for a breakthrough heart drug: learnings for cell and gene therapies.

Wed, 16 Mar 2016 00:00:00 +0100

Authors: Malik NN PMID: 26979621 [PubMed - as supplied by publisher] (Source: Regenerative Medicine)

New Gene Therapy Lights up Vision

Tue, 15 Mar 2016 15:22:30 +0100

By Drs. David Niesel and Norbert Herzog, Medical Discovery News We all need light to see, but now a new gene therapy is restoring sight to those with vision problems by figuratively lighting up their vision. Your vision cannot process anything without light. When light comes in contact with the cornea, the transparent outer layer of the eye, it bends the rays that pass through the pupil, the dark circle in the center of the eye. The purpose of the iris, the colored part of the eye, is to make the pupil bigger or smaller to let in enough but not too much light, like a camera. Behind the pupil is a lens that focuses the light on the retina in the back of the eye. The retina is composed of millions of cells, some called rods and cones for their distinctive shapes, whose purpose is to sense ...

3 Pharma Leaders on How to Use your Career to Make a Big Impact

Tue, 15 Mar 2016 07:25:49 +0100

The nominees: Guillaume Leroy, Vice President of Dengue Vaccine at Sanofi Pasteur Søren Eik Skovlund, Global Senior Manager within Global Access at Novo Nordisk Dr. Monika Lessl, VP, Head Corporate Innovation and R&D Bayer   What does it take to become a leader in pharma? Our three nominees led very different careers, but they all shared common qualities: they sought out new ways of thinking, took an interest in collaborating with the people around them, and (unfortunately for those seeking shortcuts) they had the capacity to work very, very hard. When planning out our career trajectories, many of us look to people like Guillaume, Soren and Monika as individuals to emulate. But it can also be very difficult to see the many steps it takes to get there.We sat down with our nomin...

Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia

Tue, 15 Mar 2016 00:00:00 +0100

Abstract Homozygous familial hypercholesterolemia (HoFH) is a life-threatening Mendelian disorder with a mean life expectancy of 33 years despite maximally tolerated standard lipid-lowering therapies. This disease is an ideal candidate for gene therapy, and in the last few years, a number of exciting developments have brought this approach closer to the clinic than ever before. In this review, we discuss in detail the most advanced of these developments, a recombinant adeno-associated virus (AAV) vector carrying a low-density lipoprotein receptor (LDLR) transgene which has recently entered phase 1/2a testing. We also review ongoing development of approaches to enhance transgene expression, improve the efficiency of hepatocyte transduction, and minimize the AAV capsid-specific ad...

Treating Immunodeficiency through HSC Gene Therapy.

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Booth C, Gaspar HB, Thrasher AJ Abstract Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as Z...

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The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Garcia-Huerta P, Troncoso-Escudero P, Jerez C, Hetz C, Vidal RL Abstract One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex...

Rhodopsin targeted transcriptional silencing by DNA-binding

Mon, 14 Mar 2016 00:00:00 +0100

(Source: eLife)

Gene therapy by proteasome activator, PA28γ, improves motor coordination and proteasome function in Huntington’s disease YAC128 mice

Mon, 14 Mar 2016 00:00:00 +0100

In this study, we aimed to find whether PA28γ gene transfer improves the proteasome activities and pathological symptoms in in vivo HD model. We stereotaxically injected lenti-PA28γ virus into the striatum of mutant (MT) YAC128 HD mice and littermate (LM) controls at 14–18months of age, and validated their behavioral and biochemical changes at 12weeks after the injection. YAC128 mice showed a significant increase in their peptidyl-glutamyl preferring hydrolytic (PGPH) proteasome activity and the mRNA or protein levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF after lenti-PA28γ injection. The number of ubiquitin-positive inclusion bodies was reduced in the striatum of YAC128 mice after lenti-PA28γ injection. YAC128 mice showed significant improvement of latency to fall ...

Osteogenic potential of rhBMP9 combined with a bovine‐derived natural bone mineral scaffold compared to rhBMP2

Mon, 14 Mar 2016 00:00:00 +0100

ConclusionThese results demonstrate that both rhBMP2 and rhBMP9 have osteopromotive properties on osteoblast differentiation. It was found that rhBMP9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rhBMP2 by demonstrating higher levels of ALP expression and alizarin red staining. Further animal studies comparing both recombinant proteins are necessary to further characterize the osteoinductive potential of BMP9. (Source: Clinical Oral Implants Research)

Xerostomia: Current streams of investigation

Mon, 14 Mar 2016 00:00:00 +0100

Publication date: Available online 14 March 2016 Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Ryan L. Quock Xerostomia is the subjective patient feeling of dry mouth, and it is often related to salivary hypofunction. Aside from medication-related salivary hypofunction, Sjogren’s syndrome and head-and-neck radiation are two common etiologies that have garnered considerable attention. Approaches to treating and/or preventing salivary hypofunction in patients with these conditions will likely incorporate gene therapy, stem cell therapy, and tissue engineering. Advances in these disciplines are central to current research in the cure for xerostomia and will be key to eventual treatment. Teaser Although current treatments for xerostomia may have demonstr...

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Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in L-arginine–induced acute pancreatitis in vivo

Mon, 14 Mar 2016 00:00:00 +0100

MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate gene expression by binding to the 3’ untranslated region (UTR) of target mRNAs and can be applied in gene therapy. Acute pancreatitis is an inflammatory pancreatic disease that carries considerable morbidity and mortality. The purpose of this study was to explore the therapeutic potential of microRNA-141 (miR-141) for acute pancreatitis in vivo. (Source: Pancreatology)

Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in l-arginine-induced acute pancreatitis in vivo

Mon, 14 Mar 2016 00:00:00 +0100

MicroRNAs are endogenous, non-coding RNAs of approximately 20–22 nucleotides that regulate gene expression by binding to the 3′ untranslated region (UTR) of target mRNAs and can be applied in gene therapy. Acute pancreatitis is an inflammatory pancreatic disease that carries considerable morbidity and mortality. The purpose of this study was to explore the therapeutic potential of microRNA-141 (miR-141) for acute pancreatitis in vivo. (Source: Pancreatology)

Effect of non-acoustic parameters on heterogeneous sonoporation mediated by single-pulse ultrasound and microbubbles.

Sun, 13 Mar 2016 03:31:03 +0100

Authors: Qin P, Xu L, Han T, Du L, Yu AC Abstract Sonoporation-transient plasma membrane perforation elicited by the interaction of ultrasound waves with microbubbles-has shown great potential for drug delivery and gene therapy. However, the heterogeneity of sonoporation introduces complexities and challenges in the realization of controllable and predictable drug delivery. The aim of this investigation was to understand how non-acoustic parameters (bubble related and bubble-cell interaction parameters) affect sonoporation. Using a customized ultrasound-exposure and fluorescence-imaging platform, we observed sonoporation dynamics at the single-cell level and quantified exogenous molecular uptake levels to characterize the degree of sonoporation. Sonovue microbubbles were introduced...

C-terminal amidation of PACAP-38 and PACAP-27 is dispensable for biological activity at the PAC1 receptor

Sat, 12 Mar 2016 00:00:00 +0100

Publication date: Available online 11 March 2016 Source:Peptides Author(s): Andrew C. Emery, Ryan A. Alvarez, Philip Abboud, Wenqin Xu, Craig D. Westover, Maribeth V. Eiden, Lee E. Eiden PACAP-27 and PACAP-38 are the exclusive physiological ligands for the mammalian PAC1 receptor. The role of C-terminal amidation of these ligands at that receptor was examined in neuroendocrine cells expressing the PAC1 receptor endogenously and in non-neuroendocrine cells in which the human and rat PAC1 receptors were expressed from stable single-copy genes driven by the CMV promoter, providing stoichiometrically appropriate levels of this Gs-coupled GPCR in order to examine the potency and intrinsic activity of PACAP ligands and their des-amidated congeners. We found that replacement of the C-ter...

Synthesis, characterisation and preliminary investigation of the haemocompatibility of polyethyleneimine-grafted carboxymethyl chitosan for gene delivery.

Fri, 11 Mar 2016 19:06:03 +0100

Authors: Liu X, Mo Y, Liu X, Guo R, Zhang Y, Xue W, Zhang Y, Wang C, Ramakrishna S Abstract The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. In the present study, carboxymethyl chitosan (CMCS) was prepared by chitosan (CS) alkalisation and carboxymethylation reactions. Then polyethyleneimine (PEI) was grafted to the backbone of CMCS by an amidation reaction. The CMCS-PEI copolymer showed strong complexation capability with DNA to form nanoparticles, and achieved lower cytotoxicity and higher transfection efficiency compared with PEI (25kDa) towards 293T and 3T3 cells. Moreover, the haemocompatibility of the CMCS-PEI copolymer was investigated through the aggregation, morphology and lysis of human red blood cells (RBCs), along w...

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Xalkori Approved for Rare Genetic Form of Lung Cancer

Fri, 11 Mar 2016 18:34:00 +0100

ROS-1 positive NSCLCSource: HealthDay Related MedlinePlus Page: Genes and Gene Therapy (Source: MedlinePlus Health News)

Antibody-Based Preventive and Therapeutic Strategies Against HIV.

Fri, 11 Mar 2016 02:36:02 +0100

CONCLUSION: Taking into account all the information included in this review, it seems evident that anti-HIV-1 antibodies play an important role in virus control and prevention. This review aims to give an overview of the strategies used and the advances in antibody-based preventive and therapeutic strategies against HIV-1. PMID: 26957200 [PubMed - in process] (Source: Current HIV Research)

Integrative analysis of microRNA and mRNA expression profiles in non-small-cell lung cancer

Fri, 11 Mar 2016 00:00:00 +0100

Authors: C Yang, C Sun, X Liang, S Xie, J Huang & D Li (Source: Cancer Gene Therapy)

Genetics: A New Frontier in Otology

Fri, 11 Mar 2016 00:00:00 +0100

Abstract Molecular genetics is a rapidly expanding field with possibilities for novel diagnostic and treatment strategies for otological diseases. Gene therapy, if theory is proven practical, could eliminate disease at the molecular level, thus obviating the need for pharmacologic or surgical treatment. Recent years have seen great advances in our understanding of the molecular genetic basis of many otological disorders. Building on the success of the Human Genome Project, new technologies are in development to identify disease-causing mutations through genetic testing. A basic understanding of the genetic basis of Otological diseases is crucial to the practising Otologist and the time has come for genetic services to be incorporated into regular Otological clinics. (Source: India...

Adeno‐associated virus–delivered artificial microRNA extends survival and delays paralysis in an amyotrophic lateral sclerosis mouse model

Fri, 11 Mar 2016 00:00:00 +0100

ObjectiveAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons, resulting in progressive muscle weakness, paralysis, and death within 5 years of diagnosis. About 10% of cases are inherited, of which 20% are due to mutations in the superoxide dismutase 1 (SOD1) gene. Riluzole, the only US Food and Drug Administration–approved ALS drug, prolongs survival by only a few months. Experiments in transgenic ALS mouse models have shown decreasing levels of mutant SOD1 protein as a potential therapeutic approach. We sought to develop an efficient adeno‐associated virus (AAV)‐mediated RNAi gene therapy for ALS. MethodsA single‐stranded AAV9 vector encoding an artificial microRNA against human SOD1 was injected into the cerebral lateral...

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Pilot and feasibility trial of immuno-gene therapy of malignant mesothelioma using intrapleural delivery of adenovirus- interferon-alpha combined with chemotherapy.

Fri, 11 Mar 2016 00:00:00 +0100

CONCLUSIONS: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. Overall survival rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multi-center randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. PMID: 26968202 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Blacks More Likely to Have Kidney Failure Than Whites

Thu, 10 Mar 2016 22:00:00 +0100

Researchers say high-risk gene variants that are more common in blacks don't explain the disparity Source: HealthDay Related MedlinePlus Pages: African American Health, Genes and Gene Therapy, Kidney Failure (Source: MedlinePlus Health News)

Pregnant women in favor of first maternal gene therapy trial

Thu, 10 Mar 2016 17:01:01 +0100

Stephen FellerLONDON, March 10 (UPI) -- Researchers found pregnant women are willing to participate in a trial for maternal gene therapy to treat early-onset fetal growth restriction, in a new study. (Source: Health News -

Leber Hereditary Optic Neuropathy: Bringing the Lab to the Clinic.

Thu, 10 Mar 2016 16:28:01 +0100

This article reviews the pathophysiology and clinical features of LHON with a focus on translational research. PMID: 26959136 [PubMed - as supplied by publisher] (Source: Seminars in Ophthalmology)

Course of Ocular Function in PRPF31 Retinitis Pigmentosa.

Thu, 10 Mar 2016 16:28:01 +0100

Authors: Hafler BP, Comander J, Weigel DiFranco C, Place EM, Pierce EA Abstract Mutations in pre-mRNA splicing factors are the second most common cause of autosomal dominant retinitis pigmentosa, and a major cause of vision loss. The development of gene augmentation therapy for disease caused by mutations in PRPF31 necessitates defining pretreatment characteristics and disease progression of patients with PRPF31-related retinitis pigmentosa. We show rates of decline of visual field area -6.9% per year and 30-Hz flicker cone response of -9.2% per year, which are both similar to observed rates for retinitis pigmentosa. We hypothesize that RNA splicing factor retinitis pigmentosa will be amenable to treatment by AAV-mediated gene therapy, and that understanding the clinical progressio...

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Gene therapy in the womb for ill babies

Thu, 10 Mar 2016 04:17:42 +0100

It is hoped that the genes will boost blood flow to the placenta, the lifeline between mother and baby, providing the child with the oxygen and nutrients needed to thrive and survive. (Source: the Mail online | Health)

Viruses, Vol. 8, Pages 78: A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

Thu, 10 Mar 2016 00:00:00 +0100

This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. (Source: Viruses)

Survival in glioblastoma: a review on the impact of treatment modalities

Thu, 10 Mar 2016 00:00:00 +0100

Abstract Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positiv...

Megakaryocyte- and megakaryocyte precursor-related gene therapies

Thu, 10 Mar 2016 00:00:00 +0100

Hematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual’s lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets ...

Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition

Thu, 10 Mar 2016 00:00:00 +0100

Authors: A Taura, K Taura, Y Koyama, N Yamamoto, T Nakagawa, J Ito & A F Ryan (Source: Gene Therapy)

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Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo

Thu, 10 Mar 2016 00:00:00 +0100

Authors: B E Hjelm, C Grunseich, G Gowing, P Avalos, J Tian, B C Shelley, M Mooney, K Narwani, Y Shi, C N Svendsen, J H Wolfe, K H Fischbeck & T M Pierson (Source: Gene Therapy)

Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy

Thu, 10 Mar 2016 00:00:00 +0100

Authors: T Borrás, L K Buie & M G Spiga (Source: Gene Therapy)

Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models

Thu, 10 Mar 2016 00:00:00 +0100

Authors: H Yang, T Peng, J Li, Y Wang, W Zhang, P Zhang, S Peng, T Du, Y Li, Q Yan & B Liu (Source: Gene Therapy)

Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV-1 co-regulated by differentially expressed microRNAs

Thu, 10 Mar 2016 00:00:00 +0100

Authors: K-X Zhang, Y Matsui, C Lee, O Osamu, L Skinner, J Wang, A So, P S Rennie & W W Jia (Source: Gene Therapy)

Identification of CYP4V2 Mutation in 36 Chinese Families with Bietti Crystalline Corneoretinal Dystrophy.

Thu, 10 Mar 2016 00:00:00 +0100

In this study, 43 Chinese BCD families were recruited; most patients manifested the characteristic phenotype of BCD, with 2 families initially misdiagnosed with retinitis pigmentosa. Five patients in our cohort presented with BCD and choroidal neovascularization (CNV), and 1 patient presented with typical BCD and abnormality in the terminals of both fingers and toes. A total of 17 pathogenic mutations involving 68 alleles were identified from 36 families using targeted exon sequencing and Sanger sequencing;we achieved a diagnostic rate of approximately 84%. Fifteen families were found to carry homozygous mutations, 17 families carried compound heterozygous mutations, and 4 families carried a single heterozygous mutation. Of the mutations identified, four variants c.802-8_810del17bpinsGC, c...

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Genetic improvement of olive (Olea europaea L.) by conventional and in vitro biotechnology methods.

Thu, 10 Mar 2016 00:00:00 +0100

Authors: Rugini E, Cristofori V, Silvestri C Abstract In olive (Olea europaea L.) traditional methods of genetic improvement have to now produced limited results. Intensification of olive growing requires appropriate new cultivars for fully mechanized groves, but among the large number of the traditional varieties very few are suitable. High-density and super high-density hedge row orchards require genotypes with reduced size, reduced apical dominance, a semi-erect growth habit, easy to propagate, resistant to abiotic and biotic stresses, with reliably high productivity and quality of both fruits and oil. Innovative strategies supported by molecular and biotechnological techniques are required to speed up novel hybridisation methods. Among traditional approaches the Gene Pool Metho...

Generation and usage of aequorin lentiviral vectors for Ca(2+) measurement in sub-cellular compartments of hard-to-transfect cells.

Thu, 10 Mar 2016 00:00:00 +0100

We describe methods for the production of lentiviral particles, and provide examples of measuring Ca(2+) dynamics by such aequorin-encoding lentiviral vectors in sub-cellular compartments of hard-to-transfect cells, including immortalized striatal neurons, primary cerebellar granule neurons and endothelial progenitor cells, which provide suitable in vitro models for the study of different human diseases. PMID: 26992273 [PubMed - as supplied by publisher] (Source: Cell Calcium)

Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early‐onset fetal growth restriction

Wed, 09 Mar 2016 00:00:00 +0100

ConclusionsThis study did not identify any fundamental or insurmountable objections to a trial of maternal gene therapy for severe early‐onset FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. (Source: Ultrasound in Obstetrics and Gynecology)

Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: an anatomical and behavioral analysis.

Wed, 09 Mar 2016 00:00:00 +0100

Authors: You SW, Hellström M, Pollett MA, LeVaillant C, Moses C, Rigby PJ, Penrose M, Rodger J, Harvey AR Abstract Peripheral nerve (PN) grafts can be used to bridge tissue defects in the CNS. Using a PN-to-optic nerve (ON) graft model, we combined gene therapy with pharmacotherapy to promote the long-distance regeneration of injured adult retinal ganglion cells (RGCs). Autologous sciatic nerve was sutured onto the transected ON and the distal end immediately inserted into contralateral superior colliculus (SC). Control rats received intraocular injections of saline or adeno-associated virus (AAV) encoding GFP. In experimental groups, three bi-cistronic AAV vectors encoding ciliary neurotrophic factor (CNTF) were injected into different regions of the grafted eye. Each vector enco...

Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction.

Wed, 09 Mar 2016 00:00:00 +0100

CONCLUSIONS: This study did not identify any fundamental or insurmountable objections to a trial of maternal gene therapy for severe early-onset FGR. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID: 26968870 [PubMed - as supplied by publisher] (Source: The Ultrasound Review of Obstetrics and Gynecology)

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Spark Therapeutics Buys Ireland Gene Therapy Co.

Tue, 08 Mar 2016 18:22:00 +0100

Spark Therapeutics has announced that it has acquired Dublin, Ireland-based Genable Technologies, a private gene therapy innovator. (Source:

Sleeping Beauty Transposon Vectors in Liver-directed Gene Delivery of LDLR and VLDLR for Gene Therapy of Familial Hypercholesterolemia

Tue, 08 Mar 2016 00:00:00 +0100

Authors: Tytteli A K Turunen, Jere Kurkipuro, Tommi Heikura, Taina Vuorio, Elisa Hytönen, Zsuzsanna Izsvák & Seppo Ylä-Herttuala (Source: Molecular Therapy)

Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma

Tue, 08 Mar 2016 00:00:00 +0100

Publication date: April 2016 Source:Biomedicine & Pharmacotherapy, Volume 79 Author(s): Wei Peng, Jianzhong Wu, Jifeng Feng Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Emerging studies have implicated that long noncoding RNAs (lncRNAs) are differentially expressed in various tumors and play an important role in the development of cancer. Previously, our group has reported that the novel lncRNA HULC has important biological function and clinical potential in human pancreatic cancer. Here, we investigated the expression of HULC in a cohort of DLBCL to assess its expression pattern, clinical...

Alliance for Cancer Gene Therapy announces three new grant awardees for cancer research

Mon, 07 Mar 2016 05:00:00 +0100

(Alliance for Cancer Gene Therapy) Alliance for Cancer Gene Therapy announces three new research grants into Leukemia/Lymphoma, Melanoma and Blood Cancers using cell, gene and immunotherapy. (Source: EurekAlert! - Cancer)

Why Does Aspartame Have a Warning Label?

Mon, 07 Mar 2016 00:17:01 +0100

Discussion Phenylketonuria (PKU) is an autosomal recessive genetic disease. The PAH gene is found on chromosome 12 and has more than 600 mutations associated with it. The incidence varies but PKU is primarily found in Caucasian populations. The PAH gene codes for phenylalanine hydroxylase (PAH) which catalyzes the amino acid phenylalanine (Phe) to tyrosine. PAH uses a cofactor called tetrahydrobiopterin (BH4) in this process. With a deficiency in PAH, Phe accumulates and can cause severe cognitive impairment and global developmental delay, microcephaly, seizures, poor growth and poor skin pigmentation. Tyrosine also decreases and along with it its products of melanin, L-thyroxine and catecholamine neurotransmitters. The exact cause of the PKU clinical problems may be an accumulation of Phe...

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The promise of gene therapy

Sun, 06 Mar 2016 18:07:17 +0100

Purpose of review: The promise of gene therapy performed in the preimplantation and prenatal periods of pregnancy is rapidly becoming a reality. New technologies capable of making designed changes in single nucleotides make germline gene therapy possible. The article reviews the ethical and technical challenges of germline gene therapy. Recent findings: Clustered regularly interspaced short palindromic repeats and related technologies are capable of deleting and inserting specific DNA sequences in mutated genes so as to correct the targeted DNA. The ability to target specific gene mutations will offer unique opportunities to at risk families, particularly those whose genotypes prevent any chance of a normal pregnancy outcome. Other applications of gene-modifying technologies on gametes, z...

Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity.

Sun, 06 Mar 2016 05:15:02 +0100

Authors: Wu L, Zhou WB, Shen F, Liu W, Wu HW, Zhou SJ, Li SW Abstract Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell‑cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death‑inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV‑TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans‑retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in‑vitro and in‑vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. ...

Restriction of HIV-1-based lentiviral vectors in adult primary marrow-derived and peripheral mobilized human CD34+ hematopoietic stem and progenitor cells occurs prior to viral DNA integration

Sat, 05 Mar 2016 00:00:00 +0100

Gene therapy is currently being attempted using a number of delivery vehicles including lentiviral-based vectors. The delivery and insertion of a gene using lentiviral-based vectors involves multiple discrete ... (Source: Retrovirology)

Chapter 11 Experimental therapies

Fri, 04 Mar 2016 00:00:00 +0100

Publication date: 2016 Source:Handbook of Clinical Neurology, Volume 134 Author(s): M. Maher Hulou, Choi-Fong Cho, E. Antonio Chiocca, Rolf Bjerkvig Glioblastoma is the most common and aggressive primary brain tumor in adults. Over the past three decades, the overall survival time has only improved by a few months, therefore novel alternative treatment modalities are needed to improve clinical management strategies. Such strategies should ultimately extend patient survival. At present, the extensive insight into the molecular biology of gliomas, as well as into genetic engineering techniques, has led to better decision processes when it comes to modifying the genome to accommodate suicide genes, cytokine genes, and tumor suppressor genes that may kill cancer cells, and boost the host...