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Current Gene Therapy Review Issue
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- Category: Journal Archive
- Published on Saturday, 17 July 2010 07:03
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Volume 2, July 2010
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Editorial: Gene Therapy Progress in 2009
The year 2009 was quite turbulent for gene therapy companies, with lay-offs, bankruptcies and general financial crisis. Earlier 2008 FDA refused US based Introgen’s Biologics License application (1) and during 2009 now bankrupt Introgen sold it’s GMP facilities and other remaining assets to Vivante GMP Solutions, ceasing to exist as gene therapy company. Similarly other gene therapy companies have had difficulties on getting their products to the market, especially with the economic crisis hindering their financing. After facing extensive difficulties, the path often leads to turning into a CMO, field with heavy competition.
Gene Therapy For Malignant Pleural Mesothelioma
Masatoshi Tagawa, Yuji Tada, Kenzo Hiroshima and Hideaki Shimada
Mesothelioma is relatively rare in frequency but is one of the intractable cancers linked with asbestos exposure. The patient numbers will increase in near future and current clinical outcomes with conventional treatment modalities are not satisfactory. Gene therapy is a possible therapeutic strategy because of easy accessibility of a vector system into the intrapleural cavity. Several preclinical studies demonstrated that the gene medicine produced anti-tumor effects, suggesting the clinical feasibility. In this review, we summarized the current status of clinical trials targeting mesothelioma.
Aptamer Targeting of Osteopontin in Cancer Metastasis
Syamal Bhattcharya, MD; Zhiyong MI, PhD; Hongtao Guo, MD, PhD; Paul C. Kuo, MD
In recent years a novel crop of therapies called aptamers have been derived that take advantage of small segment nucleotides that tightly bind cell surface proteins. This interaction at the extracellular level impedes the normal cascade of the receptor protein, blunting or arresting the usual chain of intracellular events. In contrast to antibody directed therapies, aptamers are able to function at very low concentrations. In addition to the robust binding capability to target cell surface proteins (as described by the dissociation constant), added benefits of aptamer therapy include exquisite target specificity and a lack of immunogenicity. When compared to antisense oligonucleotides, aptamers are superior in that the targets are extracellular.
Chromatin Insulators and Prospective Application for Gene Therapy
Armelle Gaussin and Nic Mermod
Integrating viral vectors hold great promise as gene transfer vectors for gene therapy purposes because they allow maintaining long-term expression of the therapeutic transgene throughout cell divisions. However, many issues related to integration of the provirus remain as a substantial risk for patients. The use of chromatin insulators has been proposed as a possible solution to problems raised by the integration of the vector.
Regulation of SOD3 Transgene Expression
Mikko Laukkanen
A number of different enzymes and molecules are involved in the maintenance of reduction-oxidation reaction (redox) balance in tissues. The three mammalian dismutases, cytosolic CuZnSOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular superoxide dismutase (SOD3) are among the most important redox enzymes. They differ by the cellular localization and therefore have slightly different regulation of expression and therapeutic effects in tissue damage recovery suggesting distinct targets for gene therapy. In the current review I focus on the regulation of SOD3 gene expression in tissues and on the effect of SOD3 transgene on signal transduction.
Naked DNA liver delivery by hydrodynamic injection
Maria Jose Herrero and Salvador F. Aliño
Gene therapy is a strategy in which nucleic acid is administered for therapeutic purposes for both inherited and acquired diseases. A number of viral and nonviral vectors have been developed to circumvent the barriers for gene delivery, but the safety concerns of viral vectors have not been solved yet. On the other hand, non viral vectors are still inefficient compared to viral vectors but they offer safety as the main advantage and moreover they can be easily formulated as medicines.
Use of non-integrative lentiviral vectors for gene therapy
Pierre Cordelier
Human Immunodeficiency Virus (HIV)-derived lentiviral vectors provide efficient gene transfer in proliferative and quiescent cells and demonstrate stable, high-level transgene expression both in vitro and in vivo. HIV non specifically integrates its DNA into the human genome, with a preference for active genes. However, integration can be problematic because a variation in gene expression between cells, possible gene silencing, and most importantly insertional mutagenesis, that can provoke malignant transformation. These findings clearly indicate that integration of lentiviral vectors must be prevented to ensure optimal safety.
Plasmid DNA Transfection
Michael L. Roberts
The term transfection is commonly used to describe the process of adding DNA into cells with a view to mediating protein expression of the transgene of interest. Although DNA transfection is the most commonly adopted technique, the term can also be applied to RNA transfection, where the purpose may also be to mediate protein expression or to achieve knockdown of the transcription of a specific gene, either by RNAi, ribozyme or antisense methodologies.
Special Focus on Lentiviral Vector Development & Applications
Pankaj Kumar
The recent developments of viral based vectors in design, in biosafety and in accomplishing high transfection efficiency for transgene expression into target cells makes them attractive tool for various gene transfer applications. Several kinds of viruses, including HIV derived Lentivirus vectors (LVs), non-HIV based Retroviruses, Adenoviruses, Adeno-associated viruses, Baculovirus and Herpes simplex viruses have been manipulated for use in gene transfer and gene therapy purposes. Each viral vector system is integrated with a distinctive in built properties that affect its suitability for specific gene therapy purposes. Although LVs offered many unique solutions for advanced gene therapy research and clinical applications, however, several important issues of LVs gene therapy must be overcome before it gains widespread use. Nonetheless, the number of promising gene therapy studies in progress are highly encouraging and outcome from these clinical trials will provide valuable insights particularly for the clinical suitability and safety profile of LVs. This review contain a comprehensive discussion starting with the general background of the field thereafter discussing the salient features of recent developments in viral vector system in general and with special focus on LVs.
Gene Therapy of OTC Deficiency
Orestis Argyros
Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder with an incidence rate of 1:80,000 births in Japan (1). It occurs when a mutant enzyme protein (OTC) impairs the reaction that leads to condensation of carbamoyl phosphate and ornithine to form citrulline. This impairment leads to reduced ammonia incorporation, which, in turn, causes hyperammonemia. Ammonia is especially damaging to the nervous system, so ornithine transcarbamylase deficiency causes neurological problems as well as eventual damage to the liver.
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