Epigenetic Silencing of Retroelements in Mammalian Stem Cells: a role for RNA interference?

Funded Activity Summary

Now that the human genome has been sequenced, all the genes which encode the bricks and mortar of our cells have been defined. A major question remains: how are all these genes controlled and co-ordinated? What turns them on or off at precisely the right time? In this project we wish to test whether a newly-discovered mechanism of turning genes off in plants and flies also works in mammals. If we demonstrate this mechanism then it may help us to improve gene therapy - a novel form of medical treatment in which healthy genes are used to replace defective genes in cells. Both inherited diseases, like hemophilia, and acquired diseases, like cancer, have been considered appropriate targets for gene therapies. Surprisingly, however, the promises of gene therapy have not kept up with expectations. In attempting to achieve clinically relevant results, viruses (masters of forcing infected cells to do their bidding) have been harnessed to deliver healthy genes into diseased cells. A major problem has been that the modified, safe viruses used clinically have not been efficient at achieving sustained production of healthy gene products. In examining the question of what turns gene off, we will attack the problem of sustainability of gene therapy by defining the mechanisms involved in switching gene therapy viruses off. If we can understand what switches viral genes off in cells, then we should be able to devise means to avoid the 'off switch' and thereby provide durable treatments for many types of cancer. In the studies described , we will attack this problem using a number of different, but complementary approaches.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $296,980.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Acquired disorders such as cancer, leukemia, AIDS | Congenital disorders such as hemophilia, haemoglobinopathies | Cosuppression/gene silencing | Cystic fibrosis, hyperlipidemias, diabetes | Developmental controls in mammalian embryonic stem cells | Organ and stem cell transplantation | Retrovirus-mediated gene therapy

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