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Latest Articles on Gene Therapy

Overview of latest articles and publications on gene therapy in PubMed, including Human Gene Therapy, Journal of Molecular Medicine and Journal of Gene Medicine. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.


  • [Smart therapeutics based on synthetic gene circuits].
    [Smart therapeutics based on synthetic gene circuits]. [English Abstract, Journal Article]Sheng Wu Gong Cheng Xue Bao 2017 Mar 25; 33(3):456-466.SWPeng S, Xie Z Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory me...Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

  • [Research progress of mammalian synthetic biology in biomedical field].
    [Research progress of mammalian synthetic biology in biomedical field]. [English Abstract, Journal Article]Sheng Wu Gong Cheng Xue Bao 2017 Mar 25; 33(3):436-455.SWYang L, Yin J, Wang M, et al. Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct g...Although still in its infant stage, synthetic biology has achieved remarkable development and progress during the past decade. Synthetic biology applies engineering principles to design and construct gene circuits uploaded into living cells or organisms to perform novel or improved functions, and it has been widely used in many fields. In this review, we describe the recent advances of mammalian synthetic biology for the treatment of diseases. We introduce common tools and design principles of synthetic gene circuits, and then we demonstrate open-loop gene circuits induced by different trigger molecules used in disease diagnosis and close-loop gene circuits used for biomedical applications. Finally, we discuss the perspectives and potential challenges of synthetic biology for clinical applications.

  • Inducing indel mutation in the SOX6 Gene by Zinc Finger Nuclease for gamma reactivation: An Approach towards Gene Therapy of Beta Thalassemia.
    Inducing indel mutation in the SOX6 Gene by Zinc Finger Nuclease for gamma reactivation: An Approach towards Gene Therapy of Beta Thalassemia. [Journal Article]J Cell Biochem 2017 Sep 23.JCModares M, Shariati L, Hejazi Z, et al. β-thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β-chains.Evidences show that increased HbF levels improve the symptoms in patients with β-thalas...β-thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β-chains.Evidences show that increased HbF levels improve the symptoms in patients with β-thalassemia or sickle cell anemia. In this study, ZFN technology was applied to induce a mutation in the binding domain region of SOX6 to reactivate γ-globin expression. The sequences coding for ZFP arrays were designed and sub cloned in TDH plus as a transfer vector. The ZFN expression was confirmed using Western blot analysis. In the next step, using the site-directed mutagenesis strategy through the overlap PCR,a missense mutation (D64V) was induced in the catalytic domain of the integrase gene in the packaging plasmid and verified using DNA sequencing.Then, the integrase minus lentivirus containing ZFN cassette was packaged. Transduction of K562 cells with this virus was performed.Mutation detection assay was performed. The indel percentage of the cells transducted with lenti virus containing ZFN was 31%. After 5 days of erythroid differentiation with 15µg/ml cisplatin, the levels of γ-globin mRNA were 6-fold in the cells treated with ZFN compared to untreated cells. In the meantime, the measurement of HbF expression levels was carried out using hemoglobin electrophoresis and showed the same results. Integrase minus lentivirus can provide a useful tool for efficient transient gene expression and helps avoid disadvantages of gene targeting using the native virus.The ZFN strategy applied here to induce indel on SOX6 gene in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β-thalassemia. This article is protected by copyright. All rights reserved.

  • Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2.
    Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2. [Journal Article]Synapse 2017 Sep 23.SToth K, Slosky LM, Pack TF, et al. The "brain-gut" peptide ghrelin, which mediates food-seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein-coupled receptor GHSR...The "brain-gut" peptide ghrelin, which mediates food-seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein-coupled receptor GHSR1a, and administration of ghrelin increases the rewarding properties of psychostimulants while ghrelin receptor antagonists decrease them. Additionally, the GHSR1a signals through βarrestin-2 to regulate actin/stress fiber rearrangement, suggesting βarrestin-2 participation in the regulation of actin-mediated synaptic plasticity for addictive substances like cocaine. The effects of ghrelin receptor ligands on reward strongly suggest that modulation of ghrelin signaling could provide an effective strategy to ameliorate undesirable behaviors arising from addiction. To investigate this possibility, we tested the effects of ghrelin receptor antagonism in a cocaine behavioral sensitization paradigm using DA neuron-specific βarrestin-2 KO mice. Our results show that these mice sensitize to cocaine as well as wild-type littermates. The βarrestin-2 KO mice, however, no longer respond to the locomotor attenuating effects of the GHSR1a antagonist YIL781. The data presented here suggest that the separate stages of addictive behavior differ in their requirements for βarrestin-2 and show that pharmacological inhibition of βarrestin-2 function through GHSR1a antagonism is not equivalent to the loss of βarrestin-2 function achieved by genetic ablation. These data support targeting GHSR1a signaling in addiction therapy but indicate that using signaling biased compounds that modulate βarrestin-2 activity differentially from G protein activity may be required. This article is protected by copyright. All rights reserved.

  • Advancements in the design and scalable production of viral gene transfer vectors.
    Advancements in the design and scalable production of viral gene transfer vectors. [Journal Article, Review]Biotechnol Bioeng 2017 Sep 23.BBSharon D, Kamen A The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and mult...The last 10 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders, and multiple forms of cancer, as well as prevention of infectious diseases through vaccination. With this increased interest and widespread adoption of viral vectors by clinicians and biopharmaceutical industries, there is an imperative to engineer safer and more efficacious vectors, and develop robust, scalable and cost-effective production platforms for industrialization. This review will focus on major innovations in viral vector design and production systems for three of the most widely used viral vectors: Adenovirus, Adeno-Associated Virus, and Lentivirus. This article is protected by copyright. All rights reserved.

  • Glial fibrillary acidic protein promoter determines transgene expression in satellite glial cells following intraganglionic adeno-associated virus delivery in adult rats.
    Glial fibrillary acidic protein promoter determines transgene expression in satellite glial cells following intraganglionic adeno-associated virus delivery in adult rats. [Journal Article]J Neurosci Res 2017 Sep 23.JNXiang H, Xu H, Fan F, et al. Recombinant adeno-associated viral (AAV)-mediated therapeutic gene transfer to dorsal root ganglia (DRG) is an effective and safe tool for treating chronic pain. However, AAV with various constitutivel...Recombinant adeno-associated viral (AAV)-mediated therapeutic gene transfer to dorsal root ganglia (DRG) is an effective and safe tool for treating chronic pain. However, AAV with various constitutively active promoters leads to transgene expression predominantly to neurons, while glial cells are refractory to AAV transduction in the peripheral nervous system. The present study evaluated whether in vivo satellite glial cell (SGC) transduction in the DRG can be enhanced by the SGC-specific GFAP promoter and by using shH10 and shH19, which are engineered capsid variants with Müller glia-prone transduction. Titer-matched AAV6 (as control), AAVshH10, and AAVshH19, all encoding the EGFP driven by the constitutively active CMV promoter, as well as AAV6-EGFP and AAVshH10-EGFP driven by a GFAP promoter (AAV6-GFAP-EGFP and AAVshH10-GFAP-EGFP), were injected into DRG of adult male rats. Neurotropism of gene expression was determined and compared by immunohistochemistry. Results showed that injection of AAV6- and AAVshH10-GFAP-EGFP induces robust EGFP expression selectively in SGCs, whereas injection of either AAVshH10-CMV-EGFP or AAVshH19-CMV-EGFP into DRG resulted in a similar in vivo transduction profile to AAV6-CMV-EGFP, all showing efficient transduction of sensory neurons without significant transduction of glial cell populations. Coinjection of AAV6-CMV-mCherry and AAV6-GFAP-EGFP induces transgene expression in neurons and SGCs separately. This report, together with our prior studies, demonstrates that the GFAP promoter rather than capsid tropism determines selective gene expression in SGCs following intraganglionic AAV delivery in adult rats. A dual AAV system, one with GFAP promoter and the other with CMV promoter, can efficiently express transgenes selectively in neurons versus SGCs.

  • Co-Delivery of Drugs and Genes Using Polymeric Nanoparticles for Synergistic Cancer Therapeutic Effects.
    Co-Delivery of Drugs and Genes Using Polymeric Nanoparticles for Synergistic Cancer Therapeutic Effects. [Journal Article, Review]Adv Healthc Mater 2017 Sep 22.AHLi Y, Thambi T, Lee DS Drug and gene delivery systems based on nanoparticles, microparticles and hydrogels have been widely studied for cancer treatment in the past decade. To achieve an efficient and safe delivery, selectio...Drug and gene delivery systems based on nanoparticles, microparticles and hydrogels have been widely studied for cancer treatment in the past decade. To achieve an efficient and safe delivery, selection of drug and gene delivery carrier is critical. Biocompatible polymeric nanoparticles are considerably promising carrier candidates in delivery of drugs and genes because of their unique chemical and physical properties. However, delivery of a drug or gene sometimes cannot achieve a satisfactory treatment effect. Therefore, co-delivery of dual drugs or co-delivery of a drug and a gene in a polymeric nanoparticle has attracted attention. Such co-delivery systems can overcome multi-drug resistance of chemical drugs and achieve a synergistic therapeutic effect. In this progress report, we summarize recent progress in the preparation and application of polymeric drug and gene co-delivery nanosystems. The remaining challenges and future trends in this field are also included.

  • From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders.
    From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders. [Journal Article, Review]Am J Med Genet A 2017 Sep 21.AJOchs HD, Petroni D The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular di...The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular dissection of these entities has led to the discovery of new immunologic pathways and to novel and effective disease-specific therapies. This review provides a summary of these primary immune defects categorized by clinical phenotype and molecular similarity as defined by the International Union of Immunologic Societies (IUIS) Expert Committee for PID. In this synopsis, we discuss the molecular basis of various categories of PIDs including, but not limited to, severe combined immunodeficiencies, primary antibody deficiencies, immune dysregulation syndromes, as well as defects of the innate immune system such as phagocytic abnormalities, autoinflammatory fever syndromes, and complement deficiencies. We have attempted to focus on current strategies to prevent complications, ameliorate symptoms, or cure these disorders by promptly using antimicrobial therapies, immunoglobulin replacement, and hematopoietic stem cell transplantation. In addition, we will explore novel therapies such as molecularly targeted immunosuppression with monoclonal antibodies and specific immunomodulatory agents. Finally, we address experimental therapies targeting specific molecular defects, including gene therapy and gene editing.

  • Strong antitumor efficacy of a pancreatic tumor-targeting oncolytic adenovirus for neuroendocrine tumors.
    Strong antitumor efficacy of a pancreatic tumor-targeting oncolytic adenovirus for neuroendocrine tumors. [Journal Article]Cancer Med 2017 Sep 21.CMYamamoto Y, Nagasato M, Rin Y, et al. Although oncolytic adenoviruses are promising cancer therapy agents, for effective oncolytic activity, viruses need to specifically infect and effectively replicate in cancer cells but not in normal ce...Although oncolytic adenoviruses are promising cancer therapy agents, for effective oncolytic activity, viruses need to specifically infect and effectively replicate in cancer cells but not in normal cells. We have previously identified a pancreatic cancer-targeting ligand, SYENFSA (SYE), by screening an adenovirus library displaying random peptides against human pancreatic cancer cells and reported that a survivin promoter-regulated adenovirus, displaying the SYE ligand (AdSur-SYE), provided effective oncolysis of pancreatic ductal adenocarcinoma (PDAC) in a preclinical study. As we examined the infectivity of AdSur-SYE in human surgical specimens of various pancreatic tumors, we unexpectedly found that AdSur-SYE showed high gene transduction efficiency for pancreatic neuroendocrine tumors (PNETs) as well as for PDAC, 9.1- and 6.2-fold, respectively, compared to that of the nontargeting virus (AdSur). The infectivity of both vectors was almost the same in other cancers and organs such as the pancreas. Immunostaining indicated that the cells infected with AdSur-SYE were PNET cells but not stromal cells. AdSur-SYE showed a significantly higher oncolytic potency than that of AdSur in human PNET cell lines, and intratumoral infection with AdSur-SYE completely diminished subcutaneous tumors in a murine model, in which AdSur-SYE effectively proliferated and spread. AdSur-SYE exerted a stronger oncolytic effect in primary PNET cells cocultured with mouse embryonic fibroblasts than AdSur did. Thus, AdSur-SYE shows promise as a next-generation therapy for PNET.

  • Staging in bipolar disorder: from theoretical framework to clinical utility.
    Staging in bipolar disorder: from theoretical framework to clinical utility. [Journal Article]World Psychiatry 2017 Oct; 16(3):236-244.WPBerk M, Post R, Ratheesh A, et al. Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particula...Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

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