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RNA-away liver tumours

Sun, 21st Jun 2009

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Scientists have used a genetic technique to successfully treat mice with liver tumours.

DNA fragmentWriting in the current edition of the journal Cell, Ohio State University researcher Jerry Mendell and his team describe how they have used short sequences of genetic material to block the growth of cancers.

The work was based on the finding in recent years that cells regulate the activity of their genes through the use of a family of small molecules called micro RNAs (miRs).  These work by shutting off the actions of certain genes, particularly those linked to cell growth and which are normally active only when cells need to divide or in a developing embryo.  But if the production of these micro RNAs goes awry then many of these growth-associated genes can be reactivated, which is what, scientists believe, might promote the growth of tumours.

Indeed, when researchers have studied a number of different cancers they have found that many of the micro RNAs that should be present are in fact missing in the malignant cells.  This led the Ohio team to ask what would happen if they put the micro RNAs back into cancerous cells?

To find out the researchers used experimental mice with a genetic tendency to develop liver cancers. Having identified one micro RNA that was frequently missing from the malignant cells in these mice, the team inserted the genetic sequence for that micro RNA - called miR-26a - into an adeno-associated virus vector (AAV), which is effectively a viral shell that lacks the ability to reproduce.

One group of mice were given injections into a blood vessel supplying the liver of a million million particles of the virus containing miR-26a.  A second group of mice received injections with a dummy virus and were used as controls.

Three weeks later the animals were studied for signs of liver tumours.  As expected, six out of eight of the control animals all had large liver tumours, but the team found that of the ten animals given the therapeutic virus eight had very few signs of disease.  In these animals tests showed that the virus had successfully penetrated 90% of the cells in the liver, and of the two animals that did not respond the treatment appeared to have failed because the viruses did not reach the liver successfully - in other words for technical rather than biological reasons.

Clearly it is early days, and the safety of this approach still needs to be confirmed, but this discovery, the first of its kind, shows that the future treatment of cancer most likely rests with genetics, rather than just toxic drugs.



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