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Synergistic antitumoral effect of vinblastine and HSV-Tk/GCV gene therapy mediated by albumin-associated cationic liposomes

Faneca, H.; Faustino, A.; Lima, M. C. Pedroso de
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Artigo de Revista Científica Formato: aplication/PDF
Português
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Despite recent advances in conventional therapeutic approaches for cancer, the frequently observed acquired drug resistance and toxic side effects have limited their clinical application. The main goal of this work was to investigate the combined antitumoral effect of vinblastine with HSV-Tk/GCV "suicide" gene therapy mediated by human serum albumin (HSA)-associated lipoplexes, in mammary adenocarcinoma cells (TSA cells). Our results show that, among the different lipoplex formulations tested, HSA-associated complexes prepared from EPOPC:Chol liposomes, at the (4/1) (+/-) charge ratio, was the most efficient to mediate gene delivery, even in the presence of serum. The simultaneous addition of vinblastine and HSA-EPOPC:Chol/DNA (+/-) (4/1) lipoplexes to TSA cells improved transgene expression more than 10 times. When combined with the HSV-Tk/GCV "suicide" gene therapy mediated by HSA-EPOPC:Chol/DNA (+/-) (4/1) lipoplexes, vinblastine induced a great enhancement in the antitumoral activity in TSA cells. Most importantly, this combined strategy resulted in a significant synergistic effect, thus allowing the use of a much lower dose of the drug to achieve the same therapeutic effect. Overall, our results indicate that this approach has the potential to overcome some major limitations of conventional chemotherapy...

Construção e avaliação da ação de plasmídio contendo gene suicida timidina quinase e gene imunomodulador da interleucina 12 otimizada, visando terapia gênica para carcinoma medular de tireóide; Construction and evaluation of plasmid expressing thymidine kinase suicide gene and immunomodulatory evolved interleukin-12 gene for medullary thyroid carcinoma gene therapy

Seidenberger, Katia
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 14/09/2007 Português
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Os tratamentos convencionais para carcinoma medular de tireóide (CMT) metastático são insatisfatórios. Tanto a quimioterapia quanto a radioterapia são pouco eficazes para a doença avançada. Portanto, a terapia gênica é uma promissora opção. Trabalhos de construção de vetores plasmidiais ou adenovirais específicos para cultura de células de carcinoma medular de tireóide e/ou animais têm demonstrado resultados encorajadores, conseguindo significativa redução do tumor. O objetivo deste trabalho foi construir e avaliar a eficácia do plasmídio pTCPtkevIL-12 contendo o gene da timidina quinase (HSV-tk) e da interleucina 12 otimizada/evolved (evIL-12), ambos sob controle do promotor da calcitonina modificado (TCP), visando terapia gênica do CMT. A associação entre um gene ?suicida? (TK) e um gene imunomodulador (IL12) é sabidamente sinérgica, o que motivou o emprego destes dois genes no vetor terapêutico. Por melhoramento genético, obteve-se recentemente a IL-12 otimizada/evolved, com elevada capacidade em induzir resposta imune. O promotor TCP é mais forte e mais específico que o promotor de calcitonina natural , e já foi usado em diversos trabalhos em CMT. Para determinar a atividade biológica das interleucinas 12 (evIL-12 e mIL-12)...

Terapia gênica; Gene therapy

Nardi, Nance Beyer; Teixeira, Leonardo Augusto Karam; Silva, Eduardo Filipe Avila
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
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Terapia gênica é um procedimento médico que envolve a modificação genética de células como forma de tratar doenças. Os genes influenciam praticamente todas as doenças humanas, seja pela codificação de proteínas anormais diretamente responsáveis pela doença, seja por determinar suscetibilidade a agentes ambientais que a induzem. A terapia gênica é ainda experimental, e está sendo estudada em protocolos clínicos para diferentes tipos de doenças. O desenvolvimento de métodos seguros e eficientes de transferência gênica para células humanas é um dos pontos mais importantes na terapia gênica. Apesar do grande esforço dirigido na última década para o aperfeiçoamento dos protocolos de terapia gênica humana, e dos avanços importantes na pesquisa básica, as aplicações terapêuticas da tecnologia de transferência gênica continuam ainda em grande parte teóricas. O potencial da terapia gênica é muito grande, devendo ainda causar grande impacto em todos os aspectos da medicina.; Gene therapy is a medical intervention that involves modifying the genetic material of living cells to fight disease. Genes influence virtually every human disease, either by encoding for abnormal proteins, which are directly responsible for the disease...

A role for adeno-associated viral vectors in gene therapy

Coura, Renata dos Santos; Nardi, Nance Beyer
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Gene therapy constitutes a therapeutic intervention based on modification of the genetic material of living cells, by correcting genetic defects or overexpressing therapeutic proteins. The success of gene therapy protocols depends on the availability of therapeutically suitable genes, appropriate gene delivery systems and proof of safety and efficacy. Recent advances on the development of gene delivery systems, particularly on viral vectors engineering and improved gene regulatory systems, have led to marked progress in this field. Although the available vector systems can successfully transfer genes into cells, the ideal delivery vehicle has not been found. In this context, adeno-associated virus vectors (AAV) are arising as a promising tool for a wide range of applications, due to a combination of characteristics such as lack of pathogenicity and immunogenicity, wide range of cell tropism and long-term gene expression. Since its isolation, the biological properties of the adeno-associated virus have been increasingly understood, improving our ability to manipulate and use it as a safe and efficient gene therapy vector of wide spectrum. In this work, we review the bases of gene therapy, main types of gene transfer systems and basic properties and use of AAV vectors.

Polycation-Based Gene Therapy: Current Knowledge and New Perspectives

Tiera, Marcio J.; Shi, Qin; Winnik, Francoise M.; Fernandes, Julio C.
Fonte: Bentham Science Publ Ltd Publicador: Bentham Science Publ Ltd
Tipo: Revisão Formato: 288-306
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At present, gene transfection insufficient efficiency is a major drawback of non-viral gene therapy. The 2 main types of delivery systems deployed in gene therapy are based on viral or non-viral gene carriers. Several non-viral modalities can transfer foreign genetic material into the human body. To do so, polycation-based gene delivery methods must achieve sufficient efficiency in the transportation of therapeutic genes across various extracellular and intracellular barriers. These barriers include interactions with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is a potential obstacle for functional delivery to target cells. Cationic polymers constitute one of the most promising approaches to the use of viral vectors for gene therapy. A better understanding of the mechanisms by which DNA can escape from endosomes and traffic to enter the nucleus has triggered new strategies of synthesis and has revitalized research into new polycation-based systems. The objective of this review is to address the state of the art in gene therapy with synthetic and natural polycations and the latest advances to improve gene transfer efficiency in cells.

Synthetic and natural polycations for gene therapy: State of the art and new perspectives

Tiera, M. J.; Winnik, F. M.; Fernandes, J. C.
Fonte: Bentham Science Publ Ltd Publicador: Bentham Science Publ Ltd
Tipo: Revisão Formato: 59-71
Português
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Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that. are used in gene therapy are based on viral or non-viral gene delivery systems. There are several non-viral systems that can be used to transfer foreign genetic material into the human body. In order to do so, the DNA to be transferred must escape the processes that affect the disposition of macromolecules. These processes include the interaction with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is also a potential obstacle for functional delivery to the target cell. Cationic polymers have a great potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. The objective of this review was to address the state of the art in gene therapy using synthetic and natural polycations and the latest strategies to improve the efficiency of gene transfer into the cell.

A role for adeno-associated viral vectors in gene therapy

Coura,Renata dos Santos; Nardi,Nance Beyer
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2008 Português
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65.95%
Gene therapy constitutes a therapeutic intervention based on modification of the genetic material of living cells, by correcting genetic defects or overexpressing therapeutic proteins. The success of gene therapy protocols depends on the availability of therapeutically suitable genes, appropriate gene delivery systems and proof of safety and efficacy. Recent advances on the development of gene delivery systems, particularly on viral vectors engineering and improved gene regulatory systems, have led to marked progress in this field. Although the available vector systems can successfully transfer genes into cells, the ideal delivery vehicle has not been found. In this context, adeno-associated virus vectors (AAV) are arising as a promising tool for a wide range of applications, due to a combination of characteristics such as lack of pathogenicity and immunogenicity, wide range of cell tropism and long-term gene expression. Since its isolation, the biological properties of the adeno-associated virus have been increasingly understood, improving our ability to manipulate and use it as a safe and efficient gene therapy vector of wide spectrum. In this work, we review the bases of gene therapy, main types of gene transfer systems and basic properties and use of AAV vectors.

A snapshot of gene therapy in Latin America

Linden,Rafael; Matte,Ursula
Fonte: Sociedade Brasileira de Genética Publicador: Sociedade Brasileira de Genética
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2014 Português
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65.96%
Gene therapy attempts the insertion and expression of exogenous genetic material in cells for therapeutic purposes. Conceived in the 1960s, gene therapy reached its first clinical trial at the end of the 1980s and by December 2013 around 600 genuine open clinical trials of gene therapy were registered at NIH Clinical Trials Database. Here, we summarize the current efforts towards the development of gene therapy in Latin America. Our survey shows that the number of scientists involved in the development of gene therapy and DNA vaccines in Latin America is still very low. Higher levels of investment in this technology are necessary to boost the advancement of innovation and intellectual property in this field in a way that would ease both the social and financial burden of various medical conditions in Latin America.

Theoretical Design of a Gene Therapy To Prevent AIDS but Not Human Immunodeficiency Virus Type 1 Infection

Weinberger, Leor S.; Schaffer, David V.; Arkin, Adam P.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2003 Português
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Recent reports confirm that, due to the presence of long-lived, latently infected cell populations, eradication of human immunodeficiency virus type 1 (HIV-1) from infected patients by using antiretroviral drugs will be exceedingly difficult. An alternative to virus eradication may be to use gene therapy to induce a pseudo-latent state in virus-producing cells, thus transforming HIV-1 into a lifelong, but manageable, virus. Conditionally replicating HIV-1 (crHIV-1) gene therapy vectors provide an avenue for subduing HIV-1 expression in infected cells (by creating a parasite, crHIV-1, of the parasite HIV-1), potentially reducing the HIV-1 set point and delaying AIDS onset. Development of crHIV-1 vectors has proceeded in vitro, but the requirements for a crHIV-1 vector to proliferate and persist in vivo have not been explored. We expand a widely accepted mathematical model of HIV-1 in vivo dynamics to include a crHIV-1 gene therapy virus and derive a simple criterion for designing crHIV-1 viruses that will persist in vivo. The model introduces only two new parameters—HIV-1 inhibition and crHIV-1 production—and both can be experimentally engineered and controlled. Analysis demonstrates that crHIV-1 gene therapy can indefinitely reduce HIV-1 set point to levels comparable to those achieved with highly active antiretroviral therapy...

Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy

Ravin, Suk See Ting–De; Kennedy, Douglas R.; Naumann, Nora; Kennedy, Jeffrey S.; Choi, Uimook; Hartnett, Brian J.; Linton, Gilda F.; Whiting-Theobald, Narda L.; Moore, Peter F.; Vernau, William; Malech, Harry L.; Felsburg, Peter J.
Fonte: The American Society of Hematology Publicador: The American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 15/04/2006 Português
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X-linked severe combined immunodeficiency (XSCID) is characterized by profound immunodeficiency and early mortality, the only potential cure being hematopoietic stem cell (HSC) transplantation or gene therapy. Current clinical gene therapy protocols targeting HSCs are based upon ex vivo gene transfer, potentially limited by the adequacy of HSC harvest, transduction efficiencies of repopulating HSCs, and the potential loss of their engraftment potential during ex vivo culture. We demonstrate an important proof of principle by showing achievement of durable immune reconstitution in XSCID dogs following intravenous injection of concentrated RD114-pseudotyped retrovirus vector encoding the corrective gene, the interleukin-2 receptor γ chain (γc). In 3 of 4 dogs treated, normalization of numbers and function of T cells were observed. Two long-term–surviving animals (16 and 18 months) showed significant marking of B lymphocytes and myeloid cells, normalization of IgG levels, and protective humoral immune response to immunization. There were no adverse effects from in vivo gene therapy, and in one dog that reached sexual maturity, sparing of gonadal tissue from gene transfer was demonstrated. This is the first demonstration that in vivo gene therapy targeting HSCs can restore both cellular and humoral immunity in a large-animal model of a fatal immunodeficiency.

Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy

Niemeyer, Glenn P.; Herzog, Roland W.; Mount, Jane; Arruda, Valder R.; Tillson, D. Michael; Hathcock, John; van Ginkel, Frederik W.; High, Katherine A.; Lothrop, Clinton D.
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 22/01/2009 Português
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Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)–mediated gene therapy for hemophilia B. In an 8-year study, inhibitor-prone hemophilia B dogs (n = 2) treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy (n = 3) had a bleed frequency similar to untreated FIX-deficient dogs. Coagulation tests (whole blood clotting time [WBCT], activated clotting time [ACT], and activated partial thromboplastin time [aPTT]) have remained at the upper limits of the normal ranges in the 2 dogs that received liver-directed gene therapy. The FIX activity has remained stable between 4% and 10% in both liver-treated dogs, but is undetectable in the dogs undergoing muscle-directed gene transfer. Integration site analysis by linear amplification–mediated polymerase chain reaction (LAM-PCR) suggested the vector sequences have persisted predominantly in extrachromosomal form. Complete blood count (CBC), serum chemistries, bile acid profile, hepatic magnetic resonance imaging (MRI) and computed tomography (CT) scans, and liver biopsy were normal with no evidence for tumor formation. AAV-mediated liver-directed gene therapy corrected the hemophilia phenotype without toxicity or inhibitor development in the inhibitor-prone null mutation dogs for more than 8 years.

Federal Regulation of Gene Therapy: Who Will Save our Germline?

Herdman, Karah
Fonte: Harvard University Publicador: Harvard University
Tipo: Paper (for course/seminar/workshop)
Português
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This paper will attempt to address some of these more complex issues involving human gene therapy and the encompassing regulations. The first section will deal with the science of gene therapy and will briefly touch upon the scientific hurdles that remain for scientists in this field, as this is important to understanding many of the ethical issues. This section will be divided into a basic genetic overview, a description of somatic gene therapy, and a summary of germline gene therapy. The second section will address the ethics debate that surrounds gene therapy today. Somatic gene therapy, genetic enhancements, and germline alterations are all included in this discussion. The next section will explain the current regulatory scheme that monitors human gene therapy currently in the United States. This includes an overview of the FDA and the NIH and their delegated responsibilities regarding gene therapy. Finally, the forth section of the paper will set forth a proposal in order to tackle the aforementioned scientific, ethical and legal problems.

Gene Therapy: Cure or Poison? The Proper Role of the FDA in the Bubble Boy Disease Question

Woodruff, Michele R.
Fonte: Harvard University Publicador: Harvard University
Tipo: Paper (for course/seminar/workshop)
Português
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On January 14, 2003, the Food and Drug Administration “suspended 27 gene therapy trials involving several hundred patients after learning that a second child treated in France had developed a condition resembling leukemia.†Gene therapy treats diseases caused by defective genes by introducing healthy genes into the body. For patients who are battling life-threatening diseases, the only chance of survival may be the hope of gene therapy, perhaps because there is no known cure, no available matched transplant donor, or no cures without even worse side effects. “Some of the trials being halted are intended to treat AIDS and cancer.†The “second child treated in France,†who caused the alarm, had received gene therapy treatment not for AIDS or cancer, but for the less common ailment “bubble boy disease,†a severe and fatal immunodeficiency disorder. Bubble boy disease attacks newborn boys, who while in the womb, relied on their mother’s immunity but, once born, are left helpless in fighting other diseases that attack their infant bodies. With the trials halted, parents are left helpless to seek gene therapy for their children. Is it right to eliminate alternate...

Strategies in Gene Therapy for Glioblastoma

Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S.
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
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Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.

Development of conditionally replicating integrase defective lentiviral vectors for Epstein-Barr virus gene therapy

Blasi, Maria
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
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Integrase defective lentiviral vectors show promise for achieving gene expression without integration, preserving some benefits of LVs, whereas reducing the potentially detrimental risk of insertional mutagenesis. Numerous reports supported the ability of these vectors to confer long-term gene expression in slowly dividing cell types for potentially corrective gene expression. These reports also highlighted additional applications of these vectors as delivery platforms for alternate integrative pathways, suicide gene therapy and vaccines. Nevertheless, in cell culture systems the transgene expression duration of IDLVs is highly transient, because of the rapid cell turnover, limiting their use to non-dividing or slowly dividing cells. The instability of the IDLVs in proliferating cells is mainly due to the lack of an origin of replication allowing vector’s DNA replication. In a work by Vargas et al. (2008), it has been demonstrated that if the transgene cassette carries a viral ORI, IDLV’s transgene expression persists if the necessary trans protein is supplied. In the work described in this thesis we have engineered IDLVs to selectively transduce EBNA1-expressing cells by incorporating the EBV oriP into the IDLV genome. Exploitation of EBNA1 to maintain DNA that contains the oriP has obvious use for gene therapy. Epstein–Barr virus (EBV) is widely associated with disease in both immunocompromised and immunocompetent hosts and has been implicated in approximately 1% of tumors worldwide. Current therapies are poorly effective and often toxic...

Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery.

Kremer, Karlea Lee
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2010 Português
Relevância na Pesquisa
65.97%
Gene therapy potentially holds the key for the treatment and cure of many genetic diseases, including cystic fibrosis. A number of delivery methods have been developed for the integration of a functional gene into the host genome, one of which is the use of a HIV-1 derived lentivirus, as is used in this thesis. However, a large number of issues need to be addressed before an effective gene therapy protocol can be developed, and some of these are described further in this thesis. One such issue is that the response initiated by cells to the gene transfer vector need to be addressed, as organelles such as the proteasome and lysosome that break down foreign peptides and proteins may be involved in the degradation of our gene transfer vector, ultimately limiting the amount of gene transfer vector that is able to successfully integrate into the genome. Therefore, the potential use of proteasome and lysosome inhibitors for facilitating higher levels of gene transduction in vivo was investigated. As this project uses a HIV-1 derived lentivirus for gene transfer, the use of an inhibitor of the IN1/PML innate antiretroviral response (Leptomycin B) was also assessed, again with the aim of increasing the efficiency, and hence level, of gene transfer obtained. Using a robust animal model of disease is essential for testing lentivirus constructs containing the therapeutic gene and analysing phenotypic changes in disease. A mouse model of cystic fibrosis without gastrointestinal disease was bred to obtain a robust colony of mice that efficiently produce affected mice (CFTR knockout). Visual analysis of therapeutic gene transfer in cystic fibrosis is often difficult due to the lack of antibodies available. Short DNA molecules that adopt a specific 3-D shape known as aptamers hold much potential as agents that can be developed to bind to the CFTR gene product. These can then be labelled and used in the same way as antibodies to probe tissues excised from animals treated with the therapeutic CFTR gene. Essential to gene therapy is the development of methods for the consistent determination of lentivirus titre. As the production of lentivirus becomes more sophisticated with the use of multiple transgenes in a single virus preparation...

Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression.

Stocker, Alice
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2010 Português
Relevância na Pesquisa
65.97%
Cystic Fibrosis (CF) is the most common, fatal autosomal recessive disorder affecting the Caucasian population with a frequency of 1 in 2500 live births and has a current median survival age of approximately 33 years. Characteristics of CF include abnormalities in sweat glands, malnutrition, pancreatic disease and infertility. It is however, severe and chronic lung disease that currently accounts for greater than 95% of morbidity and mortality in CF patients. The CF transmembrane conductance regulator gene was discovered in 1989 and in vitro correction of the defect soon followed, providing the basis for gene therapy as a potential cure for CF lung disease. To date, the lack of an efficient gene transfer vector system combined with the physical barriers of the airway epithelium limit the successful application of CF gene therapy. The work described in this thesis utilised a unique gene therapy approach developed by the CF Gene Therapy Research Group, which involved airway pre-treatment followed by gene delivery. Pre-treatment was with the natural detergent lysophosphatidylcholine (LPC), followed by a single-dose of a HIV-1 based lentivirus (LV) vector in vivo. Previously studies found significant gene expression within airway tissues...

Gene therapy to improve pancreatic islet transplantation for type 1 diabetes mellitus

Hughes, A.; Jessup, C.; Drogemuller, C.; Mohanasundaram, D.; Milner, C.; Rojas-Canales, D.; Russ, G.; Coates, P.
Fonte: Bentham Science Publishers Ltd. Publicador: Bentham Science Publishers Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
65.97%
Pancreatic islet transplantation is a promising treatment option for Type 1 Diabetics, offering improved glycaemic control through restoration of insulin production and freedom from life-threatening hypoglycaemic episodes. Implementation of the Edmonton protocol in 2000, a glucocorticoid-free immunosuppressive regimen has led to improved islet transplantation success. >50% of islets are lost post-transplantation primarily through cytokine-mediated apoptosis, ischemia and hypoxia. Gene therapy presents a novel strategy to modify islets for improved survival post-transplantation. Current islet gene therapy approaches aim to improve islet function, block apoptosis and inhibit rejection. Gene transfer vectors include adenoviral, adeno-associated virus, herpes simplex virus vectors, retroviral vectors (including lentiviral vectors) and non-viral vectors. Adeno-associated virus is currently the best islet gene therapy vector, due to the vectors minimal immunogenicity and high safety profile. In animal models, using viral vectors to deliver genes conferring local immunoregulation, anti-apoptotic genes or angiogenic genes to islets can significantly improve islet survival in the early post-transplant period and influence long term engraftment. With recent improvements in gene delivery and increased understanding of the mechanisms underlying graft failure...

Gene therapy

Danaher, Kerry
Fonte: Rochester Instituto de Tecnologia Publicador: Rochester Instituto de Tecnologia
Tipo: Tese de Doutorado
Português
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Many advances have been made in the study of genetics over the past decade. The ultimate goal of this research is to develop medical applications which would provide a cure for the many fatal genetically linked diseases to which conventional medicine has been only able to alleviate symptoms at best. The concept of gene therapy is based on a belief that the expression of a specific amount of functional copies of the mutated gene in the appropriate tissue could cure the disease. The Genome project is an international quest to map the entire human genome by the year 2005. This project has proven to be a major step in the science of Gene Therapy. With the mutated gene responsible for the disease located, researchers can concentrate their efforts on methods of delivering normal versions of the gene to the necessary site. This paper looks at the developments of genetics which have led to the possibility of medical application. The four diseases illustrated in this paper are among those at the forefront of genetic research. The illustrations were created with an editorial purpose in mind. They were designed for a scientific magazine which would target a general public audience. Each disease is represented by a cover illustration, as well as a descriptive illustration of the treatment procedure which would accompany the article. The articles would be part of a four month special focus on research and developments in gene therapy.

Updates on current advances in gene therapy

Tani,Jowy; Faustine,B; Sufian,Jomiany Tani
Fonte: West Indian Medical Journal Publicador: West Indian Medical Journal
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2011 Português
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66.02%
Gene therapy is the attempt to treat diseases by means of genetic manipulation. Numerous challenges remain to be overcome before it becomes available as a safe and effective treatment option. Retroviruses and adenoviruses are among the most commonly used viral vectors in trials. The retrovirus introduces the gene it carries into the target cell genome while the adenovirus introduces the gene into the target cell nucleus without incorporating it into the target cell genome. Other viral vectors such as adenoassociated viruses, pseudotyped viruses and herpes simplex viruses, are also gaining popularity. Proposed nonviral methods for gene transfer include physical methods and the employment of chemical vectors (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have investigated potential applications of gene therapy in correcting genetic diseases, treating malignant disorders and for treatment of other diseases. Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved considerable success, but the widely publicized adverse reaction in Xlinked SCID patient receiving gene therapy raised concerns for safety profile of gene therapy. For that, several methods of improving safety and efficacy of gene therapy have been proposed. At present...