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New technology could lead to safer gene therapy

EU-funded scientists have developed a new, non-viral way of getting genes into a cell. The technique appears to avoid the side-effects, such as cancer, which can occur when viruses are used to smuggle genes into a cell. The scientists hope their discovery will 'simplify the wa...

EU-funded scientists have developed a new, non-viral way of getting genes into a cell. The technique appears to avoid the side-effects, such as cancer, which can occur when viruses are used to smuggle genes into a cell. The scientists hope their discovery will 'simplify the way gene therapy is conducted, improve its overall safety and reduce the costs'. The findings, published in the journal Nature Genetics, were supported by the EU-funded JUMPY ('Transposon-based strategies for functional genomic analyses in Xenopus tropicalis, a vertebrate model system for developmental and biomedical research'), INTHER ('Development and application of transposons and site-specific integration technologies as non-viral gene delivery methods for ex vivo gene-based therapies') and PERSIST ('Persisting transgenesis') projects. Gene therapy entails the insertion of genes into a patient's cells; it has proved effective in the treatment of a number of diseases which would otherwise be untreatable. It can be used for hereditary diseases (where a healthy gene is used to replace the faulty gene the patient has inherited), as well as for diseases affecting the heart and brain. A good gene therapy technique has three characteristics: the therapeutic genes must be delivered to the right cells; the genes must remain active in the patient for a long time; and any undesired side effects should be minimised. At the moment, viruses are often used as a vector to carry the genes into the target cell. However, this approach is associated with a number of side effects, including inflammation and even the development of cancer. Furthermore, the development of the viral vectors for use in clinical trials is often hampered by technical and regulatory hurdles. In this latest study, the scientists turned to a natural gene smuggler - the transposons. Transposons are naturally occurring sections of DNA that have the ability to cut and paste themselves into foreign DNA. The researchers constructed a highly active transposon that is able to carry the therapeutic gene into the target cell and integrate it into the host's DNA. 'We show for the first time that it is now possible to efficiently deliver genes into stem cells, particularly those of the immune system, using non-viral gene delivery,' commented Marinee Chuah of the Flanders Institute for Biotechnology (VIB) in Belgium. 'Many groups have tried this for many years but without success. We are glad that we could now overcome this hurdle,' added her colleague, Thierry Vandendriessche. The researchers are now refining and testing their new-found technology for use against specific diseases, including cancer and genetic disorders. The JUMPY project received EUR 1,183,220 from the 'Quality of life and management of living resources' budget line of the Fifth Framework Programme (FP5), the INTHER project received EUR 2,800,000 from the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6), and the PERSIST project has been allocated EUR 11,181,411 under the Health Theme of the Seventh Framework Programme (FP7).

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