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RNA engineering to combat series of illnesses wins Kaye Award for Hebrew University dean

Research that has yielded success in controlling certain errors in gene expression as a safer and more effective alternative to conventional drugs has won for Prof. Hermona Soreq, dean of the Faculty of Science at the Hebrew University of Jerusalem, one of this year's Kaye Innovation Awards.

The awards, presented annually during the Hebrew University's Board of Governors meeting, were presented on June 4 during the 71st meeting of the board.

The concept behind Prof. Soreq's work lies in coping with situations involving over or under expression of certain genes. Through development of state-of-the-art technologies, she and her research partners have succeeded in manipulating the RNA that translates cholinesterase genes from DNA into the cholinesterase proteins that control body-to-brain and brain-to body communication and are therefore very important.

Essentially, all the drugs known today are aimed at blocking the activities of proteins which are in excess in the body. This, says Prof. Soreq -- who is also the Slesinger Professor of Molecular Biology at the Hebrew University is "economically" wrong, because these drugs must target a large number of molecules (the proteins). This requires relatively large quantities of the required drugs, with the accompanying danger of unwanted side effects.

On the other hand, says Prof. Soreq, one doesn't want to hamper the genes that are at the top of the "pyramid" of the process leading to the production of the proteins, because this could endanger the next generation of cells to be produced. The third possibility, she continues, is to deal with the central part of the "pyramid" the RNA level. The RNA can be cloned and engineered to be expressed in various cells or tissues, adding protein if needed. Or, conversely, the RNA can be engineered to block a particular gene from being expressed, and thus prevent production of the unwanted excess of such protein.

Prof. Soreq's invention of engineered human cholinesterase and RNA-targeted agents to suppress its functioning has been patented by Yissum, the Technology Transfer Company of the Hebrew University of Jerusalem. Over the years, this technology has won over $5 million in research grants and has generated a significant patent portfolio.

As an example of one way in which this manipulation can deal with protein excess or deficiency, Prof. Soreq cites the work being done by the PharmAthene Company in Annapolis, Maryland. This company, under license from Yissum, has developed a herd of goats which had been engineered to produce the human cholinesterase BCHE protein in their milk. PharmAthene, which has already signed a $219 million contract with the US Army to produce human BCHE for protection against nerve gas poisoning, has recently expanded its license with Yissum to include the use of BCHE for the treatment of Alzheimer's disease as well.

Another example of possible human application involves one of the protein variants produced from the closely related ACHE gene. The activity of this protein is blocked in persons who have suffered nerve gas poisoning. This human ACHE protein is now being produced under license from Yissum in engineered carrot cells developed by an Israeli company, Protalix, based in Carmiel.

A Tel Aviv startup, Ester Neurosciences, was established to exploit the promising technology developed by Prof. Soreq by developing a drug based on blocking the production of the ACHE protein in patients suffering from muscle weakening diseases.

EN101, the DNA-based lead compound utilizing this technology, has already been tested on patients with the auto-immune disease myasthenia gravis and has successfully reached phase II clinical trials. The results thus far suggest EN101 may have superior efficacy, longer duration of action, a more favorable side effect profile and dosing regimen, as compared with the currently used drug, which targets the protein. In December 2007, Ester Neurosciences was acquired by Amarin Corporation plc, a Nasdaq listed UK company.


Contact: Rebecca Zeffert
The Hebrew University of Jerusalem

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