Sustained transgene expression using non-viral enzymatic systems for stable chromosomal integration
Autor: | Dominic J. Wells, Elodie Carnus, Fabien Palazzoli, Yves Bigot |
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Rok vydání: | 2008 |
Předmět: |
Transgene
Genetic Vectors Molecular Sequence Data DNA Recombinant Gene Expression Transposases Gene delivery Biology Viral vector Recombinases Drug Discovery Genetics Recombinase Animals Chromosomes Human Humans Molecular Biology Genetics (clinical) Transposase Recombination Genetic Base Sequence Integrases Targeted Gene Repair Genetic Therapy Endonucleases Intellectual Property Meganuclease Molecular Medicine Homologous recombination |
Zdroj: | Current gene therapy. 8(5) |
ISSN: | 1566-5232 |
Popis: | Gene delivery technologies have been developed for various biotechnology applications. In gene therapy, they are promising for the treatment of several inherited and acquired human diseases. When therapies require the transfection of a transgene, the vector integration is one of the solutions that is used for maintaining and sustaining expression. On the basis of their origin, vectorisation technologies are currently divided in two fields, gathering on one hand viral vectors and, on the other hand, non-viral approaches. In the case of the non-viral therapies, three main sub-fields are in progress to integrate transgenes. The first uses oligonucleotides to stimulate targeted gene repair by homologous recombination. The second is based on site-specific endonucleases for which the cleavage activity is used to stimulate the host recombination mechanisms in the presence of a DNA vector. The third one is developed from phage and transposon enzymatic systems. The two lasts sub-fields use non-viral enzymes and are the scope of this review. Here, our objective was to overview the main non-viral enzymatic systems able to integrate DNA cassettes. Their molecular and functional characteristics are summarized, and their properties and limits in the current state of the art highlighted. An overview of the safety and quality issues is also presented and discussed, taking into account the solutions that might circumvent problems, intellectual property and economic status for each system. As a conclusion, we propose projections of the future technological developments in the context of the different interests for public and private bodies. |
Databáze: | OpenAIRE |
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