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Gene therapy is emerging as a new class of therapeutics for the treatment of inherited and acquired diseases. However, poor cellular uptake and instability of DNA in the physiological milieu limits its therapeutic potential, hence a vector which can protect and efficiently transport DNA to the target cells must be developed. Nanotechnology-based non-viral vectors have been proposed as potential candidates. Various polymeric nanoparticles have been shown to be suitable, with high cellular uptake efficiencies and reduced cytotoxicity. These delivery vectors form condensed complexes with DNA which result in shielding against enzymatic degradation and enhanced cellular targeting. Advantages including easy manipulatibility, high stability, low cost and high payload, mean that nanoparticles from various polymers have been exploited. Gene therapy gives a systematic account of the many aspects of nanotechnology mediated gene therapy, from the preparation of nanoparticles to physicochemical characterization, and follows with applications in in vitro and in vivo models. This book emphasizes the various aspects of nanotechnology-based gene therapy, with initial chapters detailing the tools and techniques available for preparation and in vitro and in vivo characterization of nanoparticles. Later chapters provide exhaustive details on polymeric systems employed for gene therapy.

• Provides an overview of nanotechnology applications in gene therapy, from preparation of nanoparticles to in vitro and in vivo studies
• Details the tools and techniques available for preparation, characterization and in vitro and in vivo study of nanoparticles
• Details the limitations of nanoparticle-mediated gene therapy and proposes ways in which they may be overcome

Gene Therapy for Viral Infections provides a comprehensive review of the broader field of nucleic acid and its use in treating viral infections. The text bridges the gap between basic science and important clinical applications of the technology, providing a systematic, integrated review of the advances in nucleic acid-based antiviral drugs and the potential advantages of new technologies over current treatment options. 

Coverage begins with the fundamentals, exploring varying topics, including harnessing RNAi to silence viral gene expression, antiviral gene editing, viral gene therapy vectors, and non-viral vectors.

Subsequent sections include detailed coverage of the developing use of gene therapy for the treatment of specific infections, the principles of rational design of antivirals, and the hurdles that currently face the further advancement of gene therapy technology.

• Provides coverage of gene therapy for a variety of infections, including HBV, HCV, HIV, hemorrhagic fever viruses, and respiratory and other viral infections
• Bridges the gap between the basic science and the important medical applications of this technology
• Features a broad approach to the topic, including an essential overview and the applications of gene therapy, synthetic RNA, and other antiviral strategies that involve nucleic acid engineering
• Presents perspectives on the future use of nucleic acids as a novel class of antiviral drugs
• Arms the reader with the cutting-edge information needed to stay abreast of this developing field

Gene therapy as a treatment for cancer is at a critical point in its evolution. Exciting new developments in gene targeting and vector technology, coupled with results from the first generation of preclinical and clinical studies have led to the design and testing of new therapeutic approaches. The Third Edition of Gene Therapy of Cancer provides crucial updates on the basic and applied sciences of gene therapy. It offers a comprehensive assessment of the field including the areas of suicide gene therapy, oncogene and suppressor gene targeting, immunotherapy, drug resistance gene therapy, and the genetic modification of stem cells. Researchers at all levels of development, from basic laboratory investigators to clinical practitioners, will find this book to be instructive.

Cancer gene therapy, like cancer therapy in general, is evolving rapidly, testing new concepts, targets and pathways, evoking new technologies, and passing new regulatory hurdles. Its essence, however, has not changed: the hope and challenges of returning altered genes to normal, using targeted gene expression to alter the function of both tumor and microenvironment, and in some cases normal cells, and delivering functionally important genes to specific cell types to increase sensitivity to killing or to protect normal cells from cancer therapies.

In some instances, gene therapy for cancer forms a continuum from gene repair through the use of molecularly modified cells; the use of viral and non-viral vector based gene delivery to both tumor and tumor microenvironment; the use of viral and gene based vaccines; and development of new gene-based therapeutics. The unique mechanistically chosen vector platforms are at the heart of this technology because they allow for direct and selective cell death and transient to sustained delivery of vaccine molecules or molecules that affect the microenvironment, vasculature, or the immune response.

• Explains the underlying cancer biology necessary for understanding proposed therapeutic approaches
• Presents in-depth description of targeting systems and treatment strategies
• Covers the breadth of gene therapy approaches including immunotherapeutic, drug resistance,oncolytic viruses, as well as regulatory perspectives from both the NCI and FDA

El parásito Echinococcus canadensis G7 (filo Platelmintos, clase Cestoda) es uno de los agentes causantes de la echinococcosis, zoonosis crónica que afecta tanto a los seres humanos como a mamíferos domésticos y salvajes, y considerada una enfermedad prioritaria por la Organización Mundial de la Salud. A pesar de su gravedad e incidencia en el mundo aún no se dispone de datos genómicos o herramientas terapéuticas y de diagnóstico eficaces para el tratamiento de la infección. La información presentada en esta tesis permite comprender características biológicas de esta especie y provee información que puede ser utilizada para el diseño de nuevas herramientas de control. En este trabajo se secuenció, ensambló y anotó el genoma de 115 Mb de E. canadensis G7. Se identificaron 11435 genes y mediante análisis de ortología se determinaron 881 grupos de genes específicos de cestodos y 581 grupos específicos del género Echinococcus. Estos análisis permitieron identificar genes que podrían ser nuevos blancos terapéuticos. Este es el primer trabajo de genómica comparativa entre las especies de Echinococcus, y mediante el cual se determinó un alto grado de variabilidad genética entre E. canadensis G7 y E. granulosus G1, a pesar de que ambas especies pertenecen al complejo E. granulosus sensu lato y presentan un fenotipo similar del estadío de metacestodo. Los análisis filogenéticos basados en el análisis de SNPs de genomas completos confirmaron a E. canadensis G7 como una especie diferente respecto a E. granulosus G1. Asimismo, se identificaron SNPs en genes del metabolismo de Echinococcus que podrían tener un impacto en su función. La validación de SNPs permitió desarrollar nuevos marcadores moleculares nucleares para diferenciar las especies de Echinococcus que infectan a animales y al hombre en Argentina, y complementan a los marcadores mitocondriales y ribosomales utilizados. Además, se analizaron tres características epigenéticas particulares: la distribución de islas CpG, el sistema de metilación del ADN y componentes de la vía de pequeños ARN basados en el análisis estructural proteína-ARN. Los resultados sugieren que Echinococcus posee mecanismos de regulación génica aún desconocidos y diferenciales entre las especies. Por otra parte, el estudio del uso de codones de Echinococcus reveló que la principal fuerza evolutiva que moldea su uso es la selección. Si bien se identificaron codones que son utilizados más frecuentemente no se encontraron diferencias entre las tres especies de Echinococcus. Los datos generados en esta tesis contribuyeron a la construcción de la base de datos WormBase ParaSite (https://parasite.wormbase.org/), especializada en parásitos platelmintos y nematodos y del Nodo Bioinformático IMPaM (http://impam2.fmed.uba.ar/) en el que se implementaron herramientas especializadas para el análisis de cestodos. La disponibilidad de un nuevo genoma es fundamental para entender la biología de un organismo patógeno, y más aún en aquellos con limitaciones para su mantenimiento y manipulación en el laboratorio.