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A realistic chance for gene therapy in the near future

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Abstract

The expanding knowledge of the genetic and cellular mechanisms of human diseases in the post-genomic era coupled with the development of different vector systems to efficiently transfer genes to a variety of cell types and organs in vivo gave rise to the concept of gene therapy as a promising therapeutic option for genetic and acquired diseases. Gene therapy has been the focus of both enthusiasm and critique in the past years. Major progress has been achieved in evaluating gene therapy in clinical trials. However, a number of hurdles must still be overcome to make gene therapy safe and applicable for human diseases. Increased knowledge of the interaction of the gene therapy vehicles with the host has resulted in modifications of existing and the development of new vector systems, as well as adjustments of future clinical applications. Adeno-associated virus vectors, retrovirus- and lentivirus-based vectors show great promise for the correction of monogenic diseases. Correction of the genetic defect can be attempted by either in vivo administration to directly target a diseased organ or by administration of ex vivo genetically modified cells, e.g., bone marrow stem cells. The lack of persistent expression and the immune responses of the host have limited the use of adenovirus vectors for the permanent correction of monogenic diseases. However, the ease of production and the number of cell types and organs that can be efficiently infected make adenovirus-based vectors a promising tool for applications where permanent gene expression is not the therapeutic goal or where the induction of immune responses is the desired response, as for genetic vaccines. Overall, gene therapy remains promising for the correction of genetic as well as acquired disorders, where permanent or transient expression of a gene product will be therapeutic.

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Acknowledgement

I thank Anja Krause for helpful discussions and critical review of the manuscript.

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  1. Department of Pediatrics and Genetic Medicine, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA

    Stefan Worgall

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Correspondence to Stefan Worgall.

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Worgall, S. A realistic chance for gene therapy in the near future. Pediatr Nephrol 20, 118–124 (2005). https://doi.org/10.1007/s00467-004-1680-0

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