It could mean cheaper drugs to treat HIV, cancer and Ebola, and enable researchers to make completely new drugs for novel medical applications.
Researchers are amending the genetic makeup of plants so that they can produce other types of drugs, such as antibodies – molecules used by our immune systems to neutralise diseases.Many of the most important drugs in modern medicine are derived from nature: aspirin from the bark of the willow tree, the pain-relief drug morphine from the opium poppy, and the powerful antimalarial drug artemisinin from the sweet wormwood plant.
Antibodies come in a great variety of types in our bodies, each of which will have a different ability to target and kill bacteria or viruses. The gene sequences encoding for certain antibodies – known to target specific, dangerous bacteria or viruses – can then be inserted into the genome of a plant, which can produce that antibody in large quantities.
‘With plants you can get to the same early stage of clinical development with a much lower financial investment,’ said Professor Julian Ma, Director of the Institute for Infection and Immunity at St George’s, University of London, UK.
‘What you need to do is to build a greenhouse – a fairly good greenhouse admittedly – probably for a tenth or even a hundredth of the cost of a typical antibody manufacturing facility,’ said Prof. Ma, who is the principal investigator of the FUTURE-PHARMA project funded by the EU's European Research Council (ERC).
‘And that means … you can take risks, you can take 10 times or 100 times more risks on a new product, because you can afford to do that (with plants).’
This lower cost would allow developing countries to produce drugs that they can't currently afford to manufacture.
Prof. Ma and his collaborator, Professor Rainer Fischer from the Fraunhofer Institute for Molecular Biology and Applied Ecology in Aachen, Germany, have used plants to produce antibodies they hope can help protect against HIV and rabies. The FUTURE-PHARMA project follows on from the EU-funded PHARMA-PLANTA project in which approval was received for the first human trial in the EU using plant-made antibodies to target HIV.
Prof. Ma believes that the technology could be adapted to produce antibodies against cancer and tuberculosis, and it is also being used to develop a treatment for Ebola.
The case of the drug ZMapp – an experimental antibody against Ebola – exemplifies the use of plants in antibody production. ZMapp is a cocktail of several antibodies that researchers have produced in tobacco plants using a strategy similar to that employed by Prof. Ma’s lab.
‘If ZMapp is a successful product and using plants is a good way of making it – the best way of making it in fact – then I’m sure this will be a springboard for the whole field,’ he said.
Natural chemicals
Researchers are not only engineering plants for antibody production, but also for the synthesis of natural chemicals with medicinal properties.
Often these compounds are made by the plants to defend against herbivores and pests and only coincidentally have medicinal properties in humans. But typically plants only need to make minute amounts of the defence compounds to gain protection, so harvesting these chemicals is cumbersome. For example, to obtain one injection’s worth of the anticancer drug taxol from its natural plant source, you would need six Pacific yew trees, each around 100 years old.
As part of the ERC-funded LIGHTDRIVENP450s project, Professor Birger Lindberg Møller at the University of Copenhagen, Denmark, is developing a way to amplify the production of valuable medicinal compounds from plants.
The idea is to alter the DNA of plant cells in a way that targets the enzymes producing these valuable compounds to the chloroplast, the sunlight-driven powerhouse of the plant cell. In this way energy production and synthesis of medicinal compounds is merged at the same place.
Prof. Møller and his team have been particularly successful in developing ways to insert certain enzymes known as P450s directly into the photosynthetic energy-producing parts of the cell in order to make plants produce diterpenoids – a class of compounds which includes the sweetener stevia, the anticancer compound taxol and forskolin, a promising anticancer compound currently used to treat glaucoma and heart failure.
‘P450s have been taken out of the chloroplast during evolution to enable the plant to prioritise energy consumption between growth, making fruits or seeds and only making defence compounds when challenged by herbivores and pests,’ said Prof. Møller. ‘Now we are putting them back and it works quite well – amazingly well actually!’
The challenges that still remain are significant, but Prof. Møller is optimistic that the technology will reach real-world application soon. ‘I would say in around five years, then I think you would have the first product from our lab with these complex molecules,’ he said.
