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Synthetic Biology Can Help Extend Anti-Malaria Drug Effectiveness
March 09, 2009In addition to providing a simple and much less expensive means of making artemisinin, the most powerful anti-malaria drug in use today, synthetic biology can also help to extend the effectiveness of this drug. Fermenting artemisinin via engineered microbes, such as yeast, can be done at far lower costs than extracting the drug from Artemsisia annua, the sweet wormwood tree, making microbial-based artemisinin a much cheaper but equally effective treatment. Restricting access to this technology to responsible manufacturers who will bundle artemisinin as part of an anti-malarial drug "cocktail" rather than selling it as a monotherapy should delay or even prevent malaria parasites from developing resistance. Recently, there have been reports of malaria parasites in West Africa showing some signs of resistance to artemisinin.
"The problem has been that some manufacturers have sold artemisinin as a monotherapy rather than as a co-therapy as is recommended by the World Health Organization," said Jay Keasling, a chemical engineer with joint appointments at Berkeley Lab and UC Berkeley, who led the development of this microbial-based method of producing artemisinin. "Any drug that is used as a monotherapy raises the possibility of microbes developing resistance to it. Right now artemisinin is grown by farmers all over the world and sold to anybody. Through the synthetic biology technique, access to the cheapest artemisinin can be restricted to manufacturers who agree to sell it as part of a co-therapy drug."
Keasling, who is one of the world's leading researchers in synthetic biology and CEO of the Joint BioEnergy Institute (JBEI), one of three U.S. Department of Energy Bioenergy Research Centers, made his remarks at a press briefing at the annual meeting of the American Association for the Advancement of Science (AAAS). At the symposium on Synthetic Life, he gave a talk entitled: Synthetic Biology in Pursuit of Low-Cost, Effective, Anti-Malarial Drugs.
"Synthetic biology is somewhat like building a computer from the off-the-shelf parts," Keasling said in his talk. "You have a knowledge base, off-the-shelf components, a system for assembling these parts and an idea as to what you want to do."
For the microbial synthesis of artemisinin, the idea started with malaria, a disease first described in 4 B.C. by Hippocrates that continues to claim the lives of more than a million victims each year, most of them children. The complex life-cycle of Plasmodium falciparum, the parasite that carries malaria, makes it impossible to eradicate the disease. Treatment is the only option and the most effective current treatment is artemisinin, which releases high doses of oxygen-based free radicals that destroy the Plasmodium parasite while it is inside a red blood cell. The cost of extracting artemisinin from wormwood trees, which only produce the drug under a narrow set of agricultural and climatological conditions, or manufacturing it entirely through chemical synthesis, is so high that impoverished populations in Africa and South America who need it the most cannot afford it.
In 2002, Keasling and members of his research group, using the tools of synthetic biology, set out to engineer a microbe that would perform most of the chemistry needed to make artemisinin in order to substantially reduce production costs. In 2003, they reported their first success. By transplanting genes from yeast and from the sweet wormwood tree into E. coli bacteria and then by-passing the E. coli's metabolic pathway and engineering a new one based on the mevalonate pathway in yeast, they were able to induce the bacteria to produce amorphadiene, a chemical precursor to artemisinin.
"Initially production was low, but we have used gene re-synthesis and other techniques to improve the yield of amorphadiene in E. coli by a millionfold from where started," Keasling said.
In 2004, Keasling received a $42.6 million grant from the Bill and Melinda Gates Foundation, through the Institute for OneWorld Health, a San Francisco-based nonprofit pharmaceutical company, to further develop his microbial artemisinin technology. A bio-tech start-up company, Amyris Biotechnologies, Inc., which is based in Emeryville, licensed the technology. In 2006, the collaboration reported the use of synthetic biology techniques to genetically engineer a strain of yeast (Saccharomyces cerevisiae) that was capable of producing high levels of artemisinic acid, the immediate precursor to artemisinin.
"Given the existence of known, relatively high-yielding chemistry for converting artemisinic acid to artemisinin or any other derivative that might be desired, microbial produced artemisinic acid is a viable source of this potent family of anti-malarial drugs," said Keasling when the yeast breakthrough was first announced.
The engineering of the yeast was a three-step process in which Keasling and his group first created a new metabolic pathway in the yeast, similar to the one created in E. coli, then introduced bacterial and wormwood genes into the yeast's DNA that interacted with the yeast's own genes to produce amorphadiene. Finally, they cloned the gene from the wormwood tree that produces the enzyme P450, which the plant uses to convert amorphadiene to artemisinic acid, and expressed it in the amorphadiene-producing yeast strain.
"We got it right the first time we tried it," Keasling said at his AAAS talk. "This is not unprecedented in the literature but it is really memorable when it happens to you!."
Last year, Keasling and his collaborators formed a new partnership with Sanofi-aventis, a leading pharmaceutical company based in France, with the goal of mass-producing low-cost microbial-based artemisinin by 2010.
"Over the long run, we expect to be able to reduce the production costs by an order of magnitude, which will fulfill our goal of meeting and beating the current cost of plant-derived artemisinin," Keasling said. "The concept is to produce artemisinin cheaply and sell it to companies that will produce the right kinds of co-therapies and enable them to compete with companies that are trying to market artemisinin as a monotherapy."
Keasling said that the same synthetic biology techniques used to make the microbial-based artemisinin should be equally effective in the drive to produce a next generation of biofuels - carbon-neutral transportation fuels derived from plant biomass.
"Artemisinin is hydrocarbon and we built a microbial platform to produce it. We can remove a few of the genes to take out artemisinin and put in a different hydrocarbon to make biofuels."
As Keasling is fond of saying, "With the tools of synthetic biology, we don't have to just accept what Nature has given us."
For more information about the Joint BioEnergy Institute visit the website at http://www.jbei.org
For more information about OneWorld Health visit the Website at http://www.oneworldhealth.org
For more information about Amyris Biotechnologies, visit the Website at http://www.amyrisbiotech.com
Lawrence Berkeley National Laboratory
"Synthetic biology is somewhat like building a computer from the off-the-shelf parts," Keasling said in his talk. "You have a knowledge base, off-the-shelf components, a system for assembling these parts and an idea as to what you want to do."
For the microbial synthesis of artemisinin, the idea started with malaria, a disease first described in 4 B.C. by Hippocrates that continues to claim the lives of more than a million victims each year, most of them children. The complex life-cycle of Plasmodium falciparum, the parasite that carries malaria, makes it impossible to eradicate the disease. Treatment is the only option and the most effective current treatment is artemisinin, which releases high doses of oxygen-based free radicals that destroy the Plasmodium parasite while it is inside a red blood cell. The cost of extracting artemisinin from wormwood trees, which only produce the drug under a narrow set of agricultural and climatological conditions, or manufacturing it entirely through chemical synthesis, is so high that impoverished populations in Africa and South America who need it the most cannot afford it.
In 2002, Keasling and members of his research group, using the tools of synthetic biology, set out to engineer a microbe that would perform most of the chemistry needed to make artemisinin in order to substantially reduce production costs. In 2003, they reported their first success. By transplanting genes from yeast and from the sweet wormwood tree into E. coli bacteria and then by-passing the E. coli's metabolic pathway and engineering a new one based on the mevalonate pathway in yeast, they were able to induce the bacteria to produce amorphadiene, a chemical precursor to artemisinin.
"Initially production was low, but we have used gene re-synthesis and other techniques to improve the yield of amorphadiene in E. coli by a millionfold from where started," Keasling said.
In 2004, Keasling received a $42.6 million grant from the Bill and Melinda Gates Foundation, through the Institute for OneWorld Health, a San Francisco-based nonprofit pharmaceutical company, to further develop his microbial artemisinin technology. A bio-tech start-up company, Amyris Biotechnologies, Inc., which is based in Emeryville, licensed the technology. In 2006, the collaboration reported the use of synthetic biology techniques to genetically engineer a strain of yeast (Saccharomyces cerevisiae) that was capable of producing high levels of artemisinic acid, the immediate precursor to artemisinin.
"Given the existence of known, relatively high-yielding chemistry for converting artemisinic acid to artemisinin or any other derivative that might be desired, microbial produced artemisinic acid is a viable source of this potent family of anti-malarial drugs," said Keasling when the yeast breakthrough was first announced.
The engineering of the yeast was a three-step process in which Keasling and his group first created a new metabolic pathway in the yeast, similar to the one created in E. coli, then introduced bacterial and wormwood genes into the yeast's DNA that interacted with the yeast's own genes to produce amorphadiene. Finally, they cloned the gene from the wormwood tree that produces the enzyme P450, which the plant uses to convert amorphadiene to artemisinic acid, and expressed it in the amorphadiene-producing yeast strain.
"We got it right the first time we tried it," Keasling said at his AAAS talk. "This is not unprecedented in the literature but it is really memorable when it happens to you!."
Last year, Keasling and his collaborators formed a new partnership with Sanofi-aventis, a leading pharmaceutical company based in France, with the goal of mass-producing low-cost microbial-based artemisinin by 2010.
"Over the long run, we expect to be able to reduce the production costs by an order of magnitude, which will fulfill our goal of meeting and beating the current cost of plant-derived artemisinin," Keasling said. "The concept is to produce artemisinin cheaply and sell it to companies that will produce the right kinds of co-therapies and enable them to compete with companies that are trying to market artemisinin as a monotherapy."
Keasling said that the same synthetic biology techniques used to make the microbial-based artemisinin should be equally effective in the drive to produce a next generation of biofuels - carbon-neutral transportation fuels derived from plant biomass.
"Artemisinin is hydrocarbon and we built a microbial platform to produce it. We can remove a few of the genes to take out artemisinin and put in a different hydrocarbon to make biofuels."
As Keasling is fond of saying, "With the tools of synthetic biology, we don't have to just accept what Nature has given us."
For more information about the Joint BioEnergy Institute visit the website at http://www.jbei.org
For more information about OneWorld Health visit the Website at http://www.oneworldhealth.org
For more information about Amyris Biotechnologies, visit the Website at http://www.amyrisbiotech.com
Lawrence Berkeley National Laboratory
Artemisinin Current Events and Artemisinin News RSSIneffective monotherapies common in high-burden malarious countries
ACTwatch, a research project led by PSI, in collaboration with the London School of Hygiene and Tropical Medicine, released evidence today that indicates that artemisinin combination therapy, the most effective medicines for treating malaria, continue to have a significantly low presence on the market among populations considered to be most at risk.
Eliminating polio requires global, coordinated effort -- Health Affairs article highlights risks, rewards of eradication
Eliminating polio everywhere will require global cooperation on several fronts, including lowering the cost for poor countries to vaccinate with inactivated polio vaccine (IPV), says a leading global health researcher in the July/August Health Affairs thematic issue on global health.
Can rapid malaria diagnostic tests improve health outcomes in practice?
A new study, carried out in primary care units in Zanzibar and published in this week's issue of PLoS Medicine, evaluates the impact of rapid malaria tests on prescribing practice and clinical outcomes.
Simple blood test proves powerful ally in the fight against malaria
Scientists at Karolinska Institutet have shown that rapid diagnostic tests (RDT) for malaria infection can provide valuable support for healthcare in low and mid-income countries in the fight against the disease.
Tools for more accurate dosage of drugs against HIV/AIDS and malaria
A doctoral thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden, shows that it is possible to describe and quantify the relationships between dose, concentration and effectiveness of several drugs against HIV/AIDS and malaria. The method may allow improved treatment and fewer undesired effects for patients with these diseases.
Novel bioreactor enhances interleukin-12 production in genetically-modified tobacco plants
Interleukin-12 is a naturally occurring protein essential for the proper functioning of the human immune system.
Applying 'supply and demand' business principles to treat infectious diseases worldwide
Treating infectious diseases while meeting escalating costs to do so continues to pose worldwide challenges, with one of the main issues being the ability to provide an adequate supply of drugs to treat infectious diseases.
Best way to treat malaria: Avoid using same drug for everyone, scientists say
A team of scientists employing a sophisticated computer model pioneered at Princeton University and Resources for the Future has found that many governments worldwide are recommending the wrong kind of malaria treatment.
Study: Delaying evolution of drug resistance in malaria parasite possible
There's no magic bullet for wiping out malaria, but a new study offers strong support for a method that effectively delays the evolution of drug resistance in malaria parasites, a University of Florida researcher says.
Discovery of key malaria proteins could mean sticky end for parasite
Scientists funded by the Wellcome Trust have identified a key mechanism that enables malaria-infected red blood cells to stick to the walls of blood vessels and avoid being destroyed by the body's immune system. The research, published today in the journal Cell, highlights an important potential new target for anti-malarial drugs.
More Artemisinin Current Events and Artemisinin News Articles
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Artemisinin 90 vcaps by NUTRICOLOGY Pure artemisinin or Qinghaosu, the active constituent of the herb Artemisia annua (sweet wormwood). Good quality Artemisia annua contains 0.3-0.5% artemisinin, so pure artemisinin provides hundreds of times more of the active constituent artemisinin than the whole herb itself. Research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract. * Picture may be of different size or flavor |
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Best Artemisinin 90 VegiCaps by Doctor's Best Science-Based Nutrition Best Artemisinin contains high quality Artemisinin or Ching-hao-su, an extract from the traditional Chinese herb Artemisia annua (sweet wormwood) or Ching-hao. Sweet wormwood leaves have been consumed over several centuries for promoting general health. The extract Artemisinin has been used for several decades. The Artemisinin used in Best Artemisinin is extracted from plants grown and harvested in accordance with GAP (Good Agricultural Practice) standards. The extract itself is manufactured to the highest pharmaceutical-grade quality specifications in a certified GMP (Good Manufacturing Practice) facility, ensuring the highest potency. |
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Artemisinin (90 Capsules) Concentrated Herbal Extract - Dietary Supplement by Get Well Natural Get Well Natural LLC's Artemisinin (a sesquiterpene lactone) is the active component isolated from the natural herb Artemisia annua (Qinghaosu) which has been long used in traditional Chinese medicine (TCM) to treat many illnesses such as multi-drug resistant strains of malaria and skin diseases.* This pure form provides a much higher concentration than the whole herb itself making the need to take hundreds of pills obsolete. Research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract.* Additional Information: Artemisinin is currently being used in early research by Henry Lai and Narenda Singh of the University of Washington for its activity against cancer as described in their published paper in Cancer Letters, 1995. *The FDA has not... |
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Artemisinin 100 mg 90 Caps by Swanson Superior Herbs More than 2,000 years ago, Chinese herbalists used a plant known as qing-haosu to strengthen the body's natural defenses. Over the centuries, use of the herb in traditional Chinese medicine declined until its immune-boosting properties were all but forgotten. Fortunately, the herb was rediscovered in the early 1970s when an archeological dig uncovered a silk scroll from the Han Dynasty describing how Artemisia leaves were used to enhance the body's resistive functions. In the years since, numerous scientific studies have supported the herb's traditional use as an immune system tonic. In fact, according to the World Health Organization, artemisinin is so effective for health concerns of the immune system that demand is outstripping supply. Now you can take advantage of this ancient herb's... |
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Allergy Research Group - Artemisinin 100 Mg, 300 Caps by Allergy Research Group Pure artemisinin or Qinghaosu, the active constituent of the herb Artemisia annua (sweet wormwood). Good quality Artemisia annua contains 0.3-0.5% artemisinin, so pure artemisinin provides hundreds of times more of the active constituent artemisinin than the whole herb itself. Research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract.Allergy Research Group introduced artemisinin to the U.S. market more than a decade ago. ARG does independent potency assays on every batch (using HPLC), and independent tests verify its effectiveness. ARG artemisinin is minimum 98.5% pure, and does not contain thujone. |
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The Use of the Herb Artemisinin for Babesia, Malaria, and Cancer: All the Practical Information You Need to Make Smart Decisions on Artemisinin by James Schaller MD (Author) This book is the only patient book written in English offering highly practical, clear, and carefully researched help on Artemisinin medications. Artemisinin herbals are powerful treatments for red blood cell infections like Malaria, and another red blood cell parasite called Babesia, which has at least eight species that infect humans and is often missed by physicians in the United States and all over the world. |
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Artemisinin by Holley Parmaceuticals Artemisinin or Qinghaosu is an extract from the plant Artemisia annua or Qinghao. Scientific research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract. FREE Shipping! |
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Allergy Research Group Artemisinin, 100mg - 90 Capsules by Allergy Research Group Pure artemisinin or Qinghaosu, the active constituent of the herb Artemisia annua (sweet wormwood). Good quality Artemisia annua contains 0.3-0.5% artemisinin, so pure artemisinin provides hundreds of times more of the active constituent artemisinin than the whole herb itself. Research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract. Allergy Research Group introduced artemisinin to the U.S. market more than a decade ago. ARG does independent potency assays on every batch (using HPLC), and independent tests verify its effectiveness. ARG artemisinin is minimum 98.5% pure, and does not contain thujone. |
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Artemisinin Gel 1 oz. 28 g. by Allergy Research - Nutricology Artemisinin Gel contains artemisinin and includes additional ingredients to facilitate absorption and effectiveness. Formulated to provide a convenient way to utilize artemisinin topically. |
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Super Artemisinin - 60 Vegetarian Capsules - Allergy Research Group by Allergy Research Group Super Artemisinin contains pure Artemisinin and oil derived from the same plant, a total of 200 mg of material per capsule. Good quality Artemisia contains 0.3-0.5% artemisinin, so pure artemisinin provides hundreds of times more of the active constituent artemisinin than the whole herb itself. ... In addition to having double the potency of our pure Artemisinin by weight, Super Artemisinin appears to be more potent. Additionally, in Chinese medicine terms, Super Artemisinin is not as cooling as artemisinin alone, and is likely to be more balanced for broad use. Research has shown artemisinin to be particularly beneficial in balancing the microbiology of the GI tract.* ... Allergy Research Group introduced Artemisinin to the U.S. market more than a decade ago and does independent potency... |
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