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Your search keyword '"gene repair"' showing total 6 results
Start Over Descriptor "gene repair" Topic genetics
6 results on '"gene repair"'

1. Progress and Prospects: targeted gene alteration (TGA).

Author

Parekh-Olmedo, H. and Kmiec, E. B.

Subjects
*GENETIC disorders, *OLIGONUCLEOTIDES, *NUCLEOTIDES, *EXCHANGE reactions, *GENETIC mutation, *GENETICS
Abstract

Targeted gene repair or targeted gene alteration is a molecular strategy that aims to correct single base mutations responsible for genetic diseases. The concept involves using single-stranded DNA oligonucleotides to direct a nucleotide exchange reaction at the genomic site of the mutation. Investigators have made significant progress in elucidating the mechanism(s) by which the mutation is corrected and have begun to focus on several viable targets that show great potential for clinical application. During the past several years, the field has witnessed a phase transition as the focus has switched from purely basic science to a sustained translational mode. We highlight the important advances over the last two to three years, some of which have moved the technology closer to the clinic while some others have introduced new reasons for caution.Gene Therapy (2007) 14, 1675–1680; doi:10.1038/sj.gt.3303053; published online 1 November 2007 [ABSTRACT FROM AUTHOR]

Published
2007
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2. A LacZ-based transgenic mouse for detection of somatic gene repair events in vivo.

Author

Nickerson, H. D. and Colledge, W. H.

Subjects
*REPAIRING, *RETROFITTING, *SYSTEM downtime, *GENETICS, *BIOLOGY, *EMBRYOLOGY
Abstract

Somatic gene repair of disease-causing chromosomal mutations is a novel approach for gene therapy. This method would ensure that the corrected gene is regulated by its endogenous promoter and expressed at physiological levels in the appropriate cell types. A reporter mouse, Gtrosa26tm1Col, was generated by targeting a mutated LacZ gene to the Rosa26 locus in mouse embryonic stem (ES) cells. The LacZ gene contains a G to A point mutation, resulting in a Glu to Lys amino-acid substitution at position 461, which abrogates enzymatic activity. The gene is expressed in ES cells, primary embryonic fibroblasts, and in all tissues examined in the adult mouse, including the lung, liver, kidney, spleen, heart, brain and smooth muscle. This transgenic mouse will allow testing of gene repair strategies in vivo and identification of which cell types can be successfully targeted by chromosomal gene repair. Although low levels of gene repair were achieved in the ES cells used to generate the Gtrosa26tm1Col mouse, preliminary attempts at gene repair in vivo were unsuccessful, thus highlighting the difficulties that will have to be overcome to get this approach to work.Gene Therapy (2004) 11, 1351-1357. doi:10.1038/sj.gt.3302311; Published online 1 July 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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3. Validation of oligonucleotide-mediated gene editing.

Author

Disterer, P., Simons, J. P., and Owen, J. S.

Subjects
*OLIGONUCLEOTIDES, *GENES, *CELLS, *NUCLEOTIDES, *PROTEINS, *GENETICS
Abstract

Several independent groups have reported targeted genomic editing in mammalian cells mediated by synthetic oligonucleotides. Nevertheless, the validity of data has been disputed because of experimental artefacts, inconsistent findings and low reproducibility. Here, we describe experiments designed to meet stringent criteria and completely eliminate artefactual results. In particular, by targeting cells expressing mutated enhanced green fluorescence protein (EGFP), which allow editing measurements at the protein level, and analyzing corrected clones by Southern blotting, we rigorously excluded spontaneous reversion, contamination artefacts, false-positives, or overestimation. Our findings provide unequivocal authentication that oligonucleotide-mediated gene editing is a real, not artefactual, phenomenon—a vital starting point from which to develop the technology into practical applications.Gene Therapy (2009) 16, 824–826; doi:10.1038/gt.2009.32; published online 2 April 2009 [ABSTRACT FROM AUTHOR]

Published
2009
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4. Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells

Author

Carmen Bertoni

Subjects
Physiology, Duchenne muscular dystrophy, ved/biology.organism_classification_rank.species, Review Article, gene repair, muscle progenitor cells, Regenerative medicine, lcsh:Physiology, Dystrophin, Genome editing, Physiology (medical), DMD, medicine, Progenitor cell, Model organism, muscle stem cell, satellite cells, Genetics, lcsh:QP1-981, biology, gene editing, ved/biology, ssODN, medicine.disease, Transplantation, gene correction, biology.protein, Stem cell, mdx, Neuroscience
Abstract

The progressive loss of muscle mass characteristic of many muscular dystrophies impairs the efficacy of most of the gene and molecular therapies currently being pursued for the treatment of those disorders. It is becoming increasingly evident that a therapeutic application, to be effective, needs to target not only mature myofibers, but also muscle progenitors cells or muscle stem cells able to form new muscle tissue and to restore myofibers lost as the result of the diseases or during normal homeostasis so as to guarantee effective and lost lasting effects. Correction of the genetic defect using oligodeoxynucleotides (ODNs) or engineered nucleases holds great potential for the treatment of many of the musculoskeletal disorders. The encouraging results obtained by studying in vitro systems and model organisms have set the groundwork for what is likely to become an emerging field in the area of molecular and regenerative medicine. Furthermore, the ability to isolate and expand from patients various types of muscle progenitor cells capable of committing to the myogenic lineage provides the opportunity to establish cell lines that can be used for transplantation following ex vivo manipulation and expansion.The purpose of this article is to provide a perspective on approaches aimed at correcting the genetic defect using gene editing strategies and currently under development for the treatment of Duchenne muscular dystrophy (DMD), the most sever of the neuromuscular disorders. Emphasis will be placed on describing the potential of using the patient own stem cell as source of transplantation and the challenges that gene editing technologies face in the field of regenerative biology.

Published
2014
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5. The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

Author

Karim Bougatef, Raja Marrakchi, Kamel Rouissi, Mohamed Cherif, Khouloud Hamdi, Slah Ouerhani, Amel Benammar Elgaaied, Islem Ben Bahria, Fethi Ben Othman, Mohamed Chebil, Mohamed Sfaxi, Nejla Stambouli, Mohamed Riadh Ben Slama, Laboratory of Genetics, Immunology and Human Pathology, Université de Tunis El Manar (UTM), Department of Urology, Hôpital Charles Nicolle [Rouen], Institut Pasteur de Tunis, and Réseau International des Instituts Pasteur (RIIP)

Subjects
Oncology, Male, MESH: Carcinoma, Pathology, Cancer Research, MESH: Nicotine, Nicotine, 0302 clinical medicine, Surgical oncology, MESH: Endonucleases, Genotype, MESH: Tobacco, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Bladder cancer, Nuclear Proteins, MESH: Neoplasm Staging, MESH: Transcription Factors, MESH: Xeroderma Pigmentosum Group D Protein, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Case-Control Studies, 3. Good health, MESH: Urinary Bladder Neoplasms, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Female, Disease Susceptibility, medicine.drug, Research Article, Gene repair, medicine.medical_specialty, Tunisia, MESH: Disease Susceptibility, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, Tobacco, Carcinoma, medicine, Genetics, Humans, Polymorphism, Gene, 030304 developmental biology, Aged, Neoplasm Staging, Xeroderma Pigmentosum Group D Protein, MESH: Humans, Case-control study, medicine.disease, Endonucleases, MESH: Male, Urinary Bladder Neoplasms, Case-Control Studies, ERCC2, MESH: Nuclear Proteins, MESH: Female, MESH: DNA-Binding Proteins, Transcription Factors
Abstract

Background In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in XPC, ERCC2 and ERCC5 genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade. Methods The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. Results Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade. Conclusion These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.

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