polymeric gene delivery review

polymeric gene delivery review - REVIEWS DESIGN AND...

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*Department of Chemical and Biomolecular Engineering, University of Illinois, Box C-3, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. Department of Bioengineering, University of Washington, Box 352255, Seattle, Washington 98195, USA. Correspondence to: D.W.P. e-mail: dpack@uiuc.edu doi:10.1038/nrd1775 Gene therapy can be defined as the treatment of human disease by the transfer of genetic material into specific cells of the patient 1 . Advances in molecular biology and biotechnology, and the completion of the Human Genome Project, have led to the identi- fication of numerous disease-causing genes. It is not difficult to envision treatment of genetic diseases such as haemophilia 2 , muscular dystrophy 3 or cystic fibro- sis 4 through replacement of errant genes within the affected cells. Gene therapies are also being developed for cardiovascular 5 , neurological 6–8 and infectious dis- eases 9 , wound healing 10 and cancer 11–13 by delivering genes to augment naturally occurring proteins, to alter the expression of existing genes, or to produce cyto- toxic proteins or prodrug-activating enzymes — for example, to kill tumour cells 11 or inhibit proliferation of endothelial cells to prevent restenosis 14 . Finally, it has been shown that expression of viral genes can result in immune responses, which has led to the concept of DNA vaccines 15 . Because of its broad potential, gene therapy has been heavily investigated during the past 15 years. The first clinical trial of gene therapy, for the treatment of severe combined immunodeficiency (SCID), was initi- ated in 1990 16 . However, it was not until April 2000 that Cavazzana-Calvo et al. reported the first clinical suc- cess with gene therapy, specifically the treatment of two infants with γ c-SCID 17 . Also that year, Kay et al. reported positive data, including increased circulating levels of factor IX, in a haemophilia clinical trial 18 and Khuri et al. reported the successful completion of a Phase II clinical trial using a combination of gene therapy and traditional chemotherapy to treat recurrent squamous- cell carcinoma of the head and neck 19 . Considering that 863 gene-therapy clinical trials have been approved worldwide since 1989 20 , the small number of successes is disappointing. Gene therapy requires the identification of a thera- peutic gene and transfer of that gene, often specifically to target cells, with high efficiency. Although short- term gene expression is sufficient for some applica- tions, such as cancer therapies, long-term expression is needed for the treatment of chronic conditions, includ- ing most genetic diseases. For many applications it will be crucial to tightly regulate gene-expression levels. Finally, one must obviously accomplish each of these tasks in a way that is safe for the patient. Both toxic- ity/pathogenicity of the delivery vehicle and immune responses to the treatment must be considered. A key limitation to development of human gene therapy remains the lack of safe, efficient and controllable methods for gene delivery 21 .
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This note was uploaded on 02/24/2010 for the course MAT 3471 taught by Professor Gashs during the Spring '10 term at Punjab Engineering College.

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polymeric gene delivery review - REVIEWS DESIGN AND...

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