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Genetically modified opium poppies could "grow" their own drugs to fight
cancer and malaria, say Australian scientists, November 2004 by Anna Salleh
.

A team led by Dr Philip Larkin from CSIRO Plant Industry reports its
research online ahead of print publication in the December issue of the
journal Nature Biotechnology.

Normal opium poppies (Papaver somniferum) are the source of the opiate drugs
morphine and codeine.

And the researchers have been tweaking genes that control the production of
these molecules to understand more about how the plant produces them, and
potentially useful precursors.

First they identified the gene that produces the enzyme for the second-last
step in the pathway that produces morphine.

Then they inserted a synthetic version of the gene that included a
modification to block that enzyme's production.

The genetic modification utilised CSIRO-patented technology for RNA
interference (or silencing). This causes a hairpin structure to form in the
RNA transcript involved in the enzyme's production.

RNA allows the genetic code to be transported around the cell and converted
into protein. The hairpin triggers a "dicer" molecule to "chew up" the
transcript thus blocking the enzyme's production.

Larkin and team found that when they blocked this second-last step in
morphine production, this caused a build up of a particular chemical earlier
on in the biochemical pathway, called reticuline.

Reticuline is a non-narcotic alkaloid that is useful in developing
antimalarial and anticancer drugs.

Earlier this year, Larkin and team did a biochemical and genetic analysis of
Norman, the naturally occurring mutant poppy that does not produce codeine
and morphine in its latex.

They identified 10 genes that play a role in preventing the poppy from
producing codeine and morphine and for leading to an accumulation of the
pharmaceutically useful precursors thebaine and oripavine.

Larkin said he now hoped to use RNA interference to switch off these 10
genes individually to see the impact on morphine production.

"It may even be that by silencing one of them we could recreate Norman," he
told ABC Science Online. "That would be very exciting." Larkin said one
advantage of creating a genetically modified version of Norman would be that
it would give scientists an opportunity to create a high-yielding version of
the poppy used to produce pain killers and drugs to treat opiate addiction.

Funding for the research came from CSIRO and Tasmanian Alkaloids, one of the
two opium poppy companies that work in Tasmania.

[abc.net.au]

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