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VATIS Update Biotechnology . Jul-Aug 2007

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Biotechnology Jul-Aug 2007

ISSN: 0971-5622

VATIS Update Biotechnology is published 4 times a year to keep the readers up to date of most of the relevant and latest technological developments and events in the field of Biotechnology. The Update is tailored to policy-makers, industries and technology transfer intermediaries.

Co-publisher: Biotech Consortium India Ltd
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Contents

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IN THE NEWS

Europe may permit GM potato cultivation

European regulators are pushing ahead with plans to allow farmers to grow a genetically modified (GM) potato but focusing first on its use in feed and non-food industries in view of the opposition from several GM-wary countries. Last December, European biotech experts failed to reach a consensus to approve the application for cultivation approval filed by German chemicals group BASF.


Normally, the application should have been sent to the environment ministers for debate within three months. Had this happened, and the ministers agreed, it would have been the first approval for growing a GM crop since 1998, when the bloc started its de facto moratorium on new biotech authorizations. But that process has been stalled, partly due to requests made to BASF for more data on its product and partly, officials say, due to reluctance inside the European Commissions environment department to push the dossier.


Now, the Commissions food safety department will ask a different experts committee to approve the cultivation of potato, engineered to yield high amounts of starch. This separate approval is also needed under European Union law. The second European Union approval relates to the potatos use in animal feed and other non-food products such as paper. By-products of the starch extraction process, like pulp, are used in animal feed and the potato juice can also be used as a soil fertilizer.


Source: www.agbios.com

EuropaBio welcomes guidance on biosimilar medicines

EuropaBio, the European association for biological industries, has welcomed the new guidance on biosimilar medicines, entitled Questions and answers on biosimilar medicines, issued by the European Agency for Evaluation of Medicines (EMEA). This new initiative reinforces the EMEA communication on biosimilar medicine and recognizes the uniqueness of these products. It states that they cannot be classified as generics due to the differences stemming from the variability of the active biotechnological substance and its manufacturing process.


EuropaBios Chair of the Healthcare Council, Dr. Andrea Rappagliosi, said: This document provides some clarification on the use of biosimilars and underscores the importance of the biosimilar regulatory pathway established in 2004. However, Mr. Thomas Bols, the Chair of EuropaBios Biosimilar Working Group, cautioned: While Europe now has an approval system in place, allowing for the introduction of biosimilars on to the market, international authorities should give guidance on a number of issues. The Q&A is a good start but other issues such as naming, interchangeability and the label of a biosimilar need to be clarified as well. (Source: www.bionity.com)
 

India allows first large-scale trials of GM food crop

India has approved the first large-scale field trials of a genetically modified (GM) food crop, a senior government official said. A Bacillus thuringiensis (Bt) variety of brinjal (aubergine), which promises better yields with less intensive use of pesticide, will be tested in the latest GM trials to be held in the country.


India has allowed commercial cultivation of GM cotton since 2002. That decision had led to large-scale protests by voluntary organizations, which said Bt cotton seeds were a health hazard and harmful for the environment. But trade experts say the new technology has pushed up production and productivity. India, the worlds second largest cotton producer after China, overtook the United States with estimated output of 28 million bales (1 bale = 170 kg) in the year to September 2007.


Source: www.news.yahoo.com

Indias laboratory market clocks 40 per cent growth

Indias laboratory chemical and equipment market is on an over drive. While the laboratory chemicals market in the country is estimated to be around US$49 million and growing at 30 per cent per year, the laboratory equipment sector is generating a turnover of US$750 million with 10 per cent growth.


The main reason for the buoyancy in the lab supplies market is the fact that Indian companies have been stepping up their R&D activity in pharmaceuticals and biotech drug development, and making inroads into global markets. Companies are also adhering to global norms and guidelines of good laboratory practices (GLP) to survive in a highly competent scenario, said Mr. V.R. Kannan, pharma consultant. In the area of lab chemicals, companies are gearing up for massive facility expansion to beat Chinese competition.


Lab equipment sector has also seen major expansion and growth. With Indian pharma-biotech companies showing an increased awareness for the need for good quality lab infrastructure, it is boom time for the business, said Mr. Amit Chatterjee, Managing Director, Sartorius India. For Waters India, the increased awareness on GLP is viewed as a great time to introduce products with superior technology and competitive pricing, stated its President, Mr. K.V. Venugoplan. For the lab equipment majors, 43 per cent of the business is generated from the R&D institutes. This is followed by analytical services 24 per cent, and quality assurance and quality control 20 per cent.


Source: www.phamabiz.com

Japanese researchers create 4G cloned pig

The research team of Dr. Hiroshi Nagashima, at the Meiji University in Tokyo, Japan, is reported to have created the worlds first fourth-generation cloned pig, an achievement that could help scientists in medical and other research. Earlier attempts to clone animals for several generations were problematic, and the scientists had thought this was because the genetic material in the nucleus of the donor cell degraded with each successive generation. But the teams findings show that a large mammal can be cloned for multiple generations in this case, the clone of a clone of a clone of a clone without degradation, just has been shown in the case of mice.


Dr. Akira Onishi, a geneticist with the Agriculture, Forestry and Fisheries Research Council, said the animal could be the worlds first fourth-generation cloned pig, an achievement that could help other cloning researchers. The results may prove important to breeders.


Source: www.straitstimes.com

MARKET NEWS

Amgen to acquire Ilypsa, focused on kidney disease

Amgen, a leader in the area of nephrology in the United States, announced that it has agreed to acquire Ilypsa, a private company developing non-absorbed drugs for renal disorders. Ilypsas lead drug candidate, ILY101, is a phosphate binder for the treatment of hyperphosphatemia in chronic kidney disease patients on haemodialysis. It is an orally administered, non-absorbed polymeric agent that prevents the absorption of ingested phosphate. Under terms of the agreement, Amgen will pay US$420 million in cash to acquire Ilypsa. After completion of the transaction, Ilypsa will become a wholly owned subsidiary of Amgen.


Ilypsa and ILY101 are a strategic fit for Amgens nephrology portfolio, said Mr. George J. Morrow, Amgens Executive Vice President of Global Commercial Operations. We are delighted to reach an agreement with Amgen that will help drive Ilypsas most promising therapeutic programme closer to commercialization, said the President and CEO of Ilypsa, Mr. Jay Shepard.


Source: www.amgen.com

Chromatin and Monsanto in agreement on gene stacking technology

Chromatin Inc. and Monsanto Company in the United States have announced a collaboration under which Monsanto has non-exclusive rights to use Chromatins mini-chromosome stacking technology in corn, cotton, soybeans and canola. Chromatin retains the right to broadly license its enabling technology so that other companies and third parties can benefit from this technology as well. Scientists from Monsanto and Chromatin will carry out a three-year programme of joint research that may be extended, as necessary, to complete the technology development.


Monsanto and Chromatin structured this non-exclusive partnership to facilitate the development of Chromatins technology for commercial and humanitarian uses, said Dr. Daphne Preuss, Chromatins Chief Scientific Officer and President. Chromatins mini-chromosome technology offers a way to stack multiple value-added traits by using a single heritable piece of the plants own DNA to deliver several genes. Monsanto will evaluate Chromatins stacking technology for use in conjunction with its existing technologies to explore more efficient methods of stacking traits.


Farmers are increasingly turning to stacked trait technologies so that they can get more benefits out of a single seed, said Dr. Robert T. Fraley, Monsanto Executive Vice President and Chief Technology Officer. Chromatins expertise in gene stacking technology will be an important resource as we look to deliver a broader variety of both input traits, such as insect and weed control, and beneficial consumer traits to improve nutrition of stacked trait options to our farmer customers, he added.


Source: www.prnewswire.com

Evogene and SunGene to collaborate on plant biotechnology

Evogene Ltd. of Israel and SunGene GmbH, a company of BASF Plant Science in Germany, have announced their collaboration to develop next generation enabling technologies for the precise bio-engineering of crops. The collaboration is supported under the Israel-Germany BioDisc programme by the Office of the Chief Scientist of the Israeli Ministry of Science and Technology and by the German Federal Ministry of Education and Research. BioDisc aims at intensifying contacts between the two countries in areas such as future technologies with high potential.


In 2006, the number of farmers growing biotech crops exceeded 10 million and the annual area of biotech crops grown exceeded 100 million hectares more than the surface area of France and Germany combined. Biotech seeds are broadly adopted in soybean, corn, cotton and canola and their sales were valued at over US$6 billion and generated over US$60 billion worth of agricultural produce. With an unprecedented 60-fold increase during the first decade of adoption, it is one of the fastest adopted technologies in recent history.
The goal of this collaboration is to enable the introduction of target genes into plant DNA in a new way by using integration sites suitable for the insertion of new genes. This will further increase efficiency in plant biotech R&D by reducing the number of plants that needs analysis. Experts in the field expect that more precise bio-engineering methodologies would significantly increase the adoption of bio-engineered crops by providing the potential to streamline and simplify the current processes.


Source: www.agbios.com

Leading companies invest in biotechnology future

Companies such as Takeda Pharmaceuticals North America, Baxter Healthcare Corporation and Astellas US have lent their support for biotechnology education and entrepreneurship in Illinois, the United States, through gifting nearly US$1 million to the iBIO Institute. The Institute is the educational arm of the Illinois Biotechnology Industry Organization, the association that champions the life sciences in Illinois and nearby Midwest.


A portion of the seed fund will support the rollout of iBIO PROPEL, a major educational programme at the University of Illinois, Chicago, designed to boost the efforts of Illinois biotechnology entrepreneurs. The purpose of the programme is to provide a boot camp educational experience for entrepreneurs, teaching them the secrets of successful start-ups, and introducing them to a wide range of resources. The programme will provide entrepreneurs with coaches seasoned start-up veterans who have taken companies through initial public offerings or major acquisitions by global firms. The coaches work with entrepreneurs to refine business strategy, prepare business plans and resolve high-level business issues.


Source: www.ibio.org

Novozymes partners Kenya Wildlife Service on biodiversity

Novozymes, Denmark, and Kenya Wildlife Service (KWS) have entered into an agreement on biological diversity. The agreement is in line with the principles of the United Nations Convention on Biological Diversity. Together, Novozymes and KWS will initiate a collaboration to characterize the microbial diversity from specific biological niches in Kenya. Under the project, Novozymes will train Kenyan students in taxonomy, isolation and identification of micro-organisms. Novozymes will transfer technology to Kenya, including know-how on collection and isolation of micro-organisms and characterization of microbial diversity.


The agreement gives Novozymes the right to make commercial use of Kenyas microbial diversity in return for financial compensation, and local institutional capacity-building. Under this agreement, if Novozymes commercializes products developed from microbial strains isolated as part of the collaborative project, KWS will receive a milestone payment and a running royalty from sales. Furthermore, Novozymes has been granted rights on similar terms to commercially make use of specific strains isolated in Kenya which are already in Novozymes possession. One minor product has already been marketed based on one of these strains. KWS will receive a payment and a royalty on any future sales. Novozymes has similar collaborations with other countries.


Source: www.bionity.com

Syngenta-IGDB collaboration in agri-biotech research

Syngenta, the global agri-biotech company, has signed a research collaboration agreement with Institute of Genetics and Developmental Biology (IGDB) in Beijing, China. The five-year agreement focuses on the identification and development of novel agronomic traits for key crops, including corn, soybean, wheat, sugar beet and sugar cane. IGDB, a part of the Chinese Academy of Sciences, is one of Chinas leading biotechnology research institutes.


Syngenta will have rights to commercialize previously and newly developed traits in the agreed range of field crops. Traits will not only be developed for the Chinese seeds market, but also for global agriculture markets. The Institute has profound discovery research in genetics, developmental biology and agricultural sciences. Its science base fits very well with Syngentas commitment to meet the high demand from farmers both inside and outside of China for new seed products, said Dr. David Lawrence, Head of R&D at Syngenta. The collaboration with Syngenta gives our Institute access to global agriculture markets through integration of new traits in the Syngenta seeds portfolio, said Dr. Yongbiao Xue, Director of IGDB.


Source: www.syngenta.com

Agilent expands genomics network in Asia-Pacific

Agilent Technologies Inc., the United States, has signed on five distributors to sell and distribute genomics products for microarray analysis. The distributors service India, Indonesia, Republic of Korea, Hong Kong, China and Australia. Agilent has also expanded its Certified Service Provider network to include ShanghaiBio Corp. in China and Genotypic Technology Ltd. in India.


Dr. Chris Tan, Agilents Director for Asia-Pacific (Genomics), explained the strategy of the company: Asia-Pacific is our strategic focus since the region has experienced double-digit growth for the last five years. We will continue to seek further collaboration with the regions top genomics customers and expand our access through highly qualified Certified Service Providers. This will help us to produce the most comprehensive portfolio of solutions and products at competitive pricing to researchers in Asia.


Source: www.bionity.com

Novozymes acquires enzyme activities of Biocon

Novozymes A/S, based in Denmark, has signed a definitive agreement under which it will acquire the enzyme activities of Biocon Ltd., Bangalore, India. The total consideration to be paid to Biocon will be the Indian Rupees equivalent of US$115 million. The purchase price has been agreed to as US$102 million, of which US$97 million will be paid upfront, and the remainder when certain specified business targets have been met. In addition, US$13 million is related to committed service fees and lease payments to be paid over a period of up to ten years.


Biocons board of directors has unanimously recommended the sale, which is subject to certain limited conditions normal in a transaction of this nature, including the approval of Biocons shareholders. Shareholders representing around 60 per cent of the total shares are reported to have committed to vote in favour of the transaction.


Source: www.bionity.com

GENOMICS

Microbial genome analysis system upgraded

Rising to accommodate the scientific communitys interest in harnessing the potential of the microbial world, the United States Department of Energys Joint Genome Institute (JGI) has made Version 2.2 of the Integrated Microbial Genomes (IMG) data management system available to the public. The new version of IMG contains a total of 2,815 genomes consisting of 687 bacteria, 41 archaea, 24 eukaryotes, 1,661 bacterial phages and 402 plasmids not associated with a specific microbial genome sequencing project. Among these genomes, 2,558 are finished and 257 are draft genomes.


IMG 2.2 also features enhanced data exploration and analysis capabilities. The data management system the result of collaboration between the JGI and Lawrence Berkeley National Laboratory Biological Data Management & Technology Centre is accessible to the public at http://img.jgi.doe. gov. IMG continues to be updated on a quarterly basis with new public and JGI genomes.


Source: www.eurekalert.org

Genomic predictors of Parkinsons disease

A collaborative study between Gene Logic Inc. and Mayo Clinic in the United States has found biomarkers that predict susceptibility to Parkinsons disease and age of disease onset. The study was novel in its detailed and comprehensive analysis of genes and their polymorphic variants across a specific biologic pathway. This work may also provide a model for the study of other complex diseases such as Alzheimers.


The researchers used sophisticated bio-informatic analysis methods to compare gene sequence variations called single nucleotide polymorphisms (SNPs) in the genomes of Parkinsons disease patients with those of their disease-free siblings. They targeted variants of genes related to the axon guidance pathway, a neural development pathway that plays an important role in the wiring of the brain during foetal development. The study methodology is claimed to open doors to more in-depth genetic understanding of complex diseases. Gene Logic provided gene expression data analysis and data interpretation, comparing the whole-genome study data to the firms Parkinsons disease gene expression knowledge base.


Source: www.bionity.com

New candidate gene for breast cancer susceptibility

In the United States, scientists at the Abramson Family Cancer Research Institute of the University of Pennsylvania and the Dana-Farber Cancer Institute have described a new candidate gene for breast-cancer susceptibility. The Rap80 gene is needed for the normal DNA-repair function of the well-known breast cancer gene BRCA1. Cancer-causing mutations in the BRCA1 protein fail to bind to the Rap80 protein. Consequently, BRCA1 is unable to identify DNA damage sites in the genome. When BRCA1 fails to fix DNA damage, cancer-causing mutations accumulate, causing the development of breast and ovarian malignancies.


In this study, the scientists found Rap80 binds to the region of the BRCA1 protein that is necessary for recognizing sites of DNA damage. Unrepaired DNA breaks can lead to cancer by increasing the rate of mutations. Modification of the cell nucleus proteins which are tightly bound to DNA by another protein called ubiquitin is responsible for signalling BRCA1 to action via Rap80. Rap80 binds to specific types of ubiquitin that concentrate at DNA damage sites.


BRCA mutations account for less than half of inherited breast cancers. The genetic basis of breast cancers in other families has been largely unknown, explains Dr. Roger Greenberg, Assistant Professor of Cancer Biology at Penn and a member of the research team. These families are unable to choose screening and treatment, the way the BRCA families can. Researchers are finding that many of these non-BRCA families have mutations in genes that have a relationship with BRCA1. In collaboration with other researchers, we are looking to see if families that have a history of breast cancer, but lack BRCA1 and BRCA2 mutations, have any gene sequence changes in Rap80, said Dr. Greenberg.


Source: www.bio.com

Gene mutation responsible for human intelligence found

Human and chimpanzee genomes are different only in 1 per cent, but that difference is hugely significant. A study carried out by researchers from the Chinese Academy of Sciences (CAS) in Kunming, has found that a certain form of neuropsin, a protein that plays a role in learning and memory, is expressed only in the central nervous systems of humans. Importantly, it seems that it originated less than 5 million years ago and scientists believe they now know the mechanism behind its production.


It has been earlier shown that type II neuropsin is not expressed in the pre-frontal cortex of lesser apes and Old World monkeys. In the new study, the scientists tested the expression of type II neuropsin in the pre-frontal cortex of chimpanzees and orangutans, and found it was not present. Since these two species diverged quite recently from human ancestors, this finding demonstrates that type II is a human-specific form that originated relatively recently.


Subsequent gene sequencing showed a mutation specific to humans that triggers a change in the splicing pattern of the neuropsin gene, creating a new splicing site and a longer protein. Introducing this mutation into chimpanzee DNA resulted in the creation of type II neuropsin. Hence, the human-specific mutation is not only necessary but also sufficient in creating the novel splice form, said study leader Dr. Bing Su. Future studies into the exact biological function of type II neuropsin could shed light into why it was positively selected for during human evolution.


Source: www.scienceagogo.com

Genetic clues to anti-malarial drug resistance

Researchers at Georgetown University Medical Centre, the United States, say they are moving closer to understanding why the most lethal form of human malaria has become resistant to drug treatment in the past three decades. They have constructed and expressed in yeast, a protozoan gene that contributes to such resistance. This gene, believed to be the largest synthetic one built, produces large quantities of the encoded protein.


The researchers, led by Prof. Paul Roepe from the Department of Biochemistry and Cellular & Molecular Biology, affirm that with PfMDR1, the recreated gene, and its protein, they have all the biomolecular tools needed to molecularly understand how Plasmodium falciparum has become resistant to most of the drugs that could once kill it. They have already described and expressed two other genes known to confer drug resistance. PfMDR1 is made up of about 4,000 base pairs and its protein is particularly large.


Chloroquine, a synthetic version of quinine, was the anti-malaria treatment of choice because it was inexpensive and needs no refrigeration. The drug works by preventing the crystallization of haeme, a toxic by-product generated when P. falciparum degrades the haemoglobin in the red cell, and which the parasite crystallizes to make it non-toxic. Isolates of P. falciparum from around the globe have developed genetic mutations that make them resistant to that drug as well as other similar agents. Parasites in different geographic regions have developed unique patterns of mutations in the three genes.
The goal now is to understand molecularly how these mutations lead to drug resistance. So far, the researchers have found that two of the three resistance genes act to change the pH (acid/alkaline balance) within the parasite when it is growing inside the red cell. These changes affect how drugs like chloroquine enter the parasite, and how efficiently they bind to pre-crystalline haeme. If these drugs cant enter blood cells as efficiently, and if the efficiency of haeme binding is pushed in the wrong direction, they cannot prevent haeme from crystallizing. The scientists, however, still dont know how the mutant proteins are controlling pH.


Source: www.biochemist.org

Genetic mutation for gastric cancer identified

Researchers at the BC Cancer Agency, Canada, have identified novel genetic mutations due to both independent mutational events and common ancestry that are linked to hereditary diffuse gastric cancer (HDGC). This type of cancer is caused by mutations in the gene CDH1, and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer.


Mr. Pardeep Kaurah and colleagues conducted a study to assess the frequency and cause of mutations in the CDH1 gene. The study included 38 families diagnosed clinically with HDGC, and 13 mutations (6 novel) were identified in 15 of the 38 families (40 per cent detection rate). Two families from this study and two additional families carrying the novel 2398delC mutation shared a common haplotype (a group of alleles of different genes on a single chromosome that are closely enough linked to be inherited usually as a unit), suggesting a founder effect (a population group with an unusual frequency of a gene owing to a small number of original members, one or more of whom had that gene). All four families originated from the southeast coast of Newfoundland.


Two branches of this family had been diagnosed with hereditary breast cancer and were tested for BRCA mutations. Within these four families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40 per cent for males and 63 per cent for females, and the risk for breast cancer in female mutation carriers was 52 per cent. The scientists concluded that 30-40 per cent of families with a family history of gastric cancer and more than 50 per cent of families with two diffuse gastric cancer cases diagnosed prior to age 50 years will carry germline mutations in the CDH1 gene.


Source: www.bio.com

Scientists identify first gene linked to scoliosis

Researchers in the United States have discovered a gene that underlies scoliosis, the abnormal curvature of the spine, which affects about 3 per cent of all children. The new finding lays the groundwork for determining how a defect in the gene known as CHD7 leads to the C- and S-shaped curves that characterize scoliosis. The genes link to scoliosis was identified by scientists at Washington University School of Medicine, working in collaboration with investigators at the University of Texas Southwestern Medical Centre and Texas Scottish Rite Hospital for Children, Rutgers State University of New Jersey and University of Iowa.


The researchers have traced a defect in CHD7 to idiopathic scoliosis, the form of the condition for which there is no apparent cause. It is the most common type of scoliosis, occurs in otherwise healthy children and is typically detected during the growth spurt that accompanies adolescence. The gene is thought to play a critical role in many basic functions in the cell. The research team zeroed in on the gene after finding that it is missing or profoundly disrupted in a rare syndrome called CHARGE. Babies born with it often die in infancy; those that survive have heart defects, mental retardation, genital and urinary problems, ear abnormalities and deafness, among other problems. They also develop late-onset scoliosis.


The researchers, led by Dr. Carol Wise of Scottish Rite Hospital, collected data on 52 families with a history of scoliosis in at least two members the one who sought treatment and another from earlier generation. The patients had an average spinal curvature of 40 and did not have any illness, such as Marfan syndrome or cerebral palsy, that can also involve scoliosis. The researchers performed genome-wide scans that spelled out the 6 billion letters of genetic code in the affected family members and analysed the data.


They found that patients with scoliosis very often had a defect in the genes non-coding region, meaning that the error did not disrupt production of the CHD7 protein. The researchers speculate that this particular mutation alters the binding of a molecule that controls whether the gene is turned on. In this case, they think the gene is turned off more often than it should be, thus reducing the amount of CHD7 protein produced. The team will continue to look for genetic variations involved in scoliosis by studying additional families with the condition.


Source: www.physorg.com

MEDICAL BIOTECH

Effective cervical cancer vaccine from plants

Vaccines against human papilloma viruses (HPV), which promise to help reduce the risk of cervical cancer, have been developed recently. However, this type of vaccine will only prevent new HPV infections, because the target of the vaccine is a protein on the surface of the virus, which is only accessible for the immune system before infection. This means that the vaccine cannot help women who already have an HPV infection.


Efforts are now under way to produce vaccines to viral proteins that are visible to the immune system once HPV has already infected a cell. These proteins, called E5, E6 and E7, are also responsible for reprogramming the host cells in such a way that they turn cancerous. This type of therapeutic vaccine would enable the immune system to eliminate an existing HPV infection and even fight cells that have turned cancerous. Vaccines based on the E7 protein have been tested successfully in animal models and are now in an advanced stage of clinical trials.


Scientists at the Fraunhofer Centre for Molecular Biotechnology, the United States, and the Italian National Agency for New Technologies, Energy and the Environment (ENEA) have tested plant-produced E7 as a vaccine in an animal model. Previous experiments had demonstrated that a plant-produced E7-vaccine could trigger immune responses in mice, and pre-treatment with the vaccine protected most of the mice from tumour formation after injection of tumour cells that produce the E7 target protein.


The researchers have also found a more efficient way to produce the E7 protein in plants by incorporating the E7 protein into a bacterial protein called LicKM. LicKM-E7 fusion protein provoked a stronger immune response in mice compared to E7 alone. The use of this patented, carrier-protein ensures that the E7 protein can be produced in high amounts and increases its stability. In the cancer model, tumour protection was also enhanced in mice vaccinated with the LicKM-E7 vaccine.


Source: www.checkbiotech.org

New light on development of insulin-producing cells

A key aspect of how embryos create the cells that secrete insulin is revealed in a new study by scientists from Imperial College London and an INSERM Unit at Necker Hospital, Paris. The study reveals the key role that glucose plays in enabling healthy beta cells, which secrete insulin, to develop in the pancreas of an embryo. Glucose prompts a gene called Neurogenin3 to switch on another gene, known as NeuroD, which is crucial for the normal development of beta cells. If glucose levels are low this gene is not switched on.


The researchers reached their conclusions after conducting research on tissues cultured from the primordial pancreas of very young rat embryos. The scientists hope that understanding how to switch on the gene that produces beta cells could eventually enable them to create these cells from stem cells and transplant them into patients with type 1 diabetes. In this type of diabetes the immune system attacks patients beta cells and at the moment few patients with the condition are able to have beta cell transplants, because the cells have to be taken from deceased donors.


Source: www.bioresearchonline.com

Modified mushrooms may yield human drugs

Mushrooms might serve as biological factories for the production of various beneficial human drugs, according to plant pathologists who have inserted new genes into mushrooms. Mushrooms could make the ideal vehicle for the manufacture of biopharmaceuticals to treat a broad array of human illnesses. But nobody has been able to come up with a feasible way of doing that, said Dr. Charles Peter Romaine, professor of plant pathology at Penn State University. Dr. Romaine and his colleague Dr. Xi Chen developed a technique to genetically modify Agaricus bisporus the button mushroom, which is the predominant edible species worldwide. One application of their technology is the use of transgenic mushrooms as factories for producing therapeutic proteins, such as vaccines, monoclonal antibodies, and hormones like insulin, or commercial enzymes, such as cellulase for biofuels.


To create transgenic mushrooms, researchers attached a gene that confers resistance to hygromycin, an antibiotic, to circular pieces of bacterial DNA called plasmids, which have the ability to multiply within Agrobacterium. The hygromycin resistance gene is a marker gene to help sort out the transgenic mushroom cells from the non-transgenic cells. The researchers then snipped small pieces off the mushrooms gill tissue and added it to a flask containing the altered bacterium. Over the course of several days, as the bacterium went through its lifecycle, it transferred a portion of its plasmid out of its cell right into the mushroom cell, and integrated the introduced gene into the chromosome of the mushroom. Next, the researchers exposed the mushroom cells to hygromycin. The antibiotic killed all the normal cells, separating out those that have been genetically altered for resistance.


The test demonstrates that if a second gene, insulin for example, were to be patched in the plasmid, that gene would be expressed as well. The degree of gene expression ultimately depends on where exactly the imported gene lands in the mushroom chromosome, among a complexity of other factors, but researchers point out that the process of producing biopharmaceuticals can be faster and cheaper with mushrooms than conventional technologies, as a crop from which drugs may be extracted could be ready in weeks. A mushroom-based biofactory also would not need expensive infrastructure set up by major drug companies.


Source: www.sciencedaily.com

New vaccine to stall African meningitis epidemics

Trials of a new meningitis vaccine have shown it to be much more effective in boosting immunity than currently available vaccines, according to researchers. It could be available in Africa within the next two to three years, said Dr. F. Marc LaForce, director of the Meningitis Vaccine Project (MVP), the group that conducted the study.
In the trial, involving 601 children between 12-23 months old in Mali and the Gambia, a single dose of the vaccine the Meningococcal conjugate vaccine reportedly produced an antibody response that was almost 20 times higher than that obtained with the older polysaccharide vaccines. The two older polysaccharide vaccines are not effective in children under two years old, they cant induce herd immunity, and they provide protection for only 2-3 years.


The new vaccine was shown to be safe in this age group. The researchers expect that it will prevent infection from Meningococcus strain A, and when a majority of people are vaccinated, it should protect entire populations, including unvaccinated people, in a phenomenon known as herd immunity. Protection is expected to last for several years, reports the MVP, and will be used to prevent epidemics, rather than dispensed reactively to control outbreaks as the older vaccines are.


Source: www.scidev.net

Largest ever study of genetics of common diseases

In the United Kingdom, the Wellcome Trust Case Control Consortium has revealed the genetics behind common diseases such as rheumatoid arthritis, diabetes and coronary heart disease. The study, the largest of its kind to date, examined DNA samples from 17,000 people across the country, and analysed almost 10 billion pieces of genetic information. It has substantially increased the number of genes known to play a role in the development of some of our most common diseases. Many of these genes that have been found are in areas of the genome not previously thought to have been related to the diseases.


Among the most significant new findings are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohns disease. For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2. The study has also confirmed the importance of a process known as autophagy self eating, responsible for clearing unwanted material (such as bacteria) from within cells in the development of Crohns disease. This may be key to the interaction of gut bacteria in inflammatory bowel disease and could have clinical significance in the future. The link between type 1 diabetes and Crohns disease is one of the most exciting findings to come out of the Consortium, says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes.


Research from the Consortium has already played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes. It has found a major gene region on chromosome 9 identified by independent studies on coronary heart disease. Further analysis as part of the Consortium will be looking at tuberculosis, breast cancer, autoimmune thyroid disease, multiple sclerosis, etc.


Source: www.biochemist.org

Substance in tree bark could lead to new cancer treatment

Researchers at University of Texas Southwestern Medical Centre, the United States, have determined how a compound, called beta-lapachone, from the bark of the South American lapacho tree kills certain kinds of cancer cells. The substance has shown promising anti-cancer properties and is currently being used in a clinical trial to examine its effectiveness against pancreatic cancer in humans. A study has now explained how beta-lapachone functions.


Dr. David Boothman, a professor in the Harold C. Simmons Comprehensive Cancer Centre and senior author of the study, and colleagues found that beta-lapachone interacts with an enzyme called NQO1, which is present at high levels in non-small cell lung cancer (NSCLC) and other solid tumours. The compound is metabolized by NQO1 and produces cell death without damaging non-cancerous tissues that do not express this enzyme. In healthy cells, NQO1 is either not present or is expressed at low levels. In contrast, certain cancer cells like NSCLC overexpress the enzyme.


Beta-lapachone also disrupts the cancer cells ability to repair its DNA, ultimately leading to the cells demise. Applying radiation to tumour cells causes DNA damage, which results in a further boost in the amount of NQO1 in the cells. Dr. Boothman tested dosing on human tumour cells using a synthesized version of beta-lapachone and found that a high dose of the compound given for only two to four hours caused all the NQO1-containing cancer cells to die. Understanding how beta-lapachone selectively kills chemotherapy-resistant tumour cells creates a new paradigm for the care of patients with NSCLC, said the researchers.


Source: www.medicalnewstoday.com

Salmonella-based vaccine against aerosolized anthrax

A joint effort by scientists from the United States and elsewhere has resulted in the development of an orally administered Salmonella-based vaccine that protects mice against aerosolized anthrax and may also have human implications. Currently, there is an effective anthrax vaccine, but it needs multiple injections over several months, is costly to produce and is not openly available.


The researchers produced Salmonella enterica serovar Typhimurium, expressing differing levels of the needed protective antigen to induce anthrax immunity and orally immunized groups of mice. Following immunization, the mice were challenged with aerosolized anthrax spores. Five of the six mice that received the vaccine containing full expression of the antigen were protected against infection, while the vaccine with reduced antigen levels only provided up to 25 per cent protection.


Website: www.bio.com

Development of insulin-producing cells

A study, by researchers from Imperial College London and an INSERM Unit at Necker Hospital in Paris, has revealed how embryos create the cells that secrete insulin. The research reveals that glucose plays a key role in enabling healthy beta cells, which secrete insulin, to develop in the pancreas of an embryo.
 

Glucose prompts a gene called Neurogenin3 to switch on another gene, known as NeuroD, which is crucial for the normal development of beta cells. If the glucose levels are low this gene is not switched on.


Knowing how to switch on the gene that produces beta cells could eventually enable researchers to create these cells from stem cells and transplant them into patients with type 1 diabetes. In this type of diabetes, the immune system destroys patients beta cells. At present, only very few patients with the condition are able to have beta cell transplants, because the cells have to be taken from deceased donors. The research may also help scientists to eventually develop drug therapies that enhance the action of glucose and thus encourage the growth of healthy beta cells.


Website: www.bio.com


PROTEOMICS

Colon cancer proteins show promise for blood test

Searching for less invasive screening tests for cancer, scientists at Johns Hopkins University, the United States, have discovered proteins present in blood that accurately identify colon cancer and pre-cancerous polyps. Initial studies of the proteins, CCSA-3 and CCSA-4, suggest they could be used to develop a blood test to identify at-risk individuals. Current screening guidelines for healthy people call for a baseline colonoscopy at age 50, followed by re-screening at least every five to 10 years. Colonoscopy is not foolproof; cancers can develop between screenings.


The two blood-dwelling proteins, first discovered by Dr. Robert Getzenberg and colleagues at the University of Pittsburgh, are thought to be remnants of cellular debris cast-off from dead cancer cells. Although the proteins roles are not entirely clear, the Johns Hopkins scientists say they are part of the scaffolding that supports structures within cell nucleus. Alteration of such nuclear scaffolding is a hallmark of cancer cells that is easily detectable under the microscope as a misshapen and discoloured nucleus. That led Dr. Getzenberg, who is currently a professor of urology and director of research at Johns Hopkins Brady Urological Institute, to the notion that there must be something at the molecular level that would form a molecular flag for cancer via a blood test.


To find the flag, Dr. Getzenbergs team drew blood samples from 107 apparently healthy individuals the day before their scheduled colonoscopies, and from 28 colorectal cancer patients. Using a particular concentration of scaffold-proteins as a marker for disease, the team was 100 per cent accurate in identifying the 28 existing cancers. Using the same protein markers, investigators also correctly identified 51 of 53 individuals (96.2 per cent) with normal colons and 14 of 18 (77.8 per cent) people with advanced pre-cancerous polyps. When researchers combined samples, they correctly identified 42 of 46 (91.3 per cent) with both cancers and advanced pre-cancerous polyps, proving the efficacy of the proteins in correctly assessing cancers.


Source: www.bio.com

Prions role in preventing Alzheimers

Normal prions produced by the body could help prevent the plaques that build up in the brain to cause Alzheimers disease. The discovery was made by a team of scientists led by Professor Nigel Hooper at the University of Leeds, United Kingdom. Alzheimers and diseases like variant Creutzfeldt-Jakob Disease (vCJD) follow similar patterns of disease progression, and in some forms of prion disease share genetic features. These parallels prompted Prof. Hoopers team to look for a link between the different conditions.


They found an apparent role for normal prion proteins in preventing Alzheimers disease. Normal prion proteins found in brain cells reduce the formation of beta-amyloid, a protein that binds with others to build brain plaques that are found in Alzheimers disease. In vCJD, the normal version of prion protein, PrPc, found naturally in the brain is corrupted by infectious prions to cause disease, explains Prof. Hooper. Using cells grown in the lab, the team looked at the effect of high and low levels of PrPC on the formation of beta-amyloid. They found that beta-amyloid did not form in cells with higher than usual levels of PrPc. When the level of PrPc was low or absent, beta-amyloid formation was found to go back up again.


It appears that PrPc exerts its beneficial effect by stopping an enzyme called beta-secretase from cutting up amyloid protein into the smaller beta-amyloid fragments needed to build plaques. Further evidence for the protective role of normal prion proteins is provided by mutated versions that are linked to genetic forms of prion disease because beta-amyloid fragments are able to form when the normal prion protein is corrupted by genetic mutation.


Source: www.biochemist.org

Fusion protein to arrest cancer

Researchers at the University of Oklahoma, the United States, have developed a protein that can stop the spread of certain cancer cells without damaging normal cells. The fusion protein prevents some types of cancer cells from ingesting a vital protein called methionine. It does not affect normal cells because, unlike cancer cells, they can remain healthy without that protein.


Chemotherapy and radiation therapies kill normal cells along with cancer cells. Dr. Roger Harrison created a mechanism that delivers these compounds specifically to the surface of cancer, said Dr. Thomas Pento, a member of the research team, which found the fusion protein to be just as helpful in fighting lung, prostate and pancreatic cancers. Despite successful testing up to this point, Dr. Harrison said the fusion protein will need another round of animal tests before moving on to years of human clinical testing.


Source: www.sci-tech-today.com

Nanoparticle-protein pairing

A groundbreaking research has demonstrated the ability to strategically attach gold nanoparticles to proteins, to form sheets of protein-gold arrays. The research, conducted at the United States Department of Energys Brookhaven National Laboratory (BNL), demonstrates that nanoparticles are appealing templates for assembling functional biomolecules.


In the field of energy conversion, scientists have been searching for efficient ways to convert organic fuels such as ethanol into electricity using catalytic enzyme electrodes. However, making single layers of densely packed enzymes has been a challenge. For this research, the scientists attached gold nanoparticles to an enzyme complex that helps drug-resistant tuberculosis bacteria survive. The researchers suggest that gold nanoparticles might also be tailored to inactivate this enzyme complex, thereby thwarting drug-resistant tuberculosis.


Previous studies by BNL have suggested that modified forms of adenovirus, a virus that causes the common cold, could be used as vehicles to deliver drugs to specific target cells, such as those that make up tumours. One key to this approach would be to enhance strong binding to the target cells. For this, the researchers attached multiple viral proteins to the gold nanoparticles. Such constructs would increase binding affinity for target cells and their larger size would extend blood residence time for improved drug delivery.


In another application, this new research showed that gold nanoparticles can enhance scientists ability to decipher the structures and functionally important regions of protein molecules. With added nanoparticles, the signal-to-noise ratio and resolution of an imaging technique known as cryo-electron microscopy were significantly increased. This method might enable analysis of small biological macromolecules and complexes that are currently intractable to analyse by cryo-electron microscopy or X-ray crystallography.


Source: www.physorg.com

RNA mystery decoded for better drug therapies

At the University of Maryland, the United States, a team of scientists has made a discovery that will help better direct drug therapies to their molecular targets. The scientists, led by Dr. Jonathan Dinman, have found the difference between two closely related components in the messenger RNA (mRNA) near-cognate and non-cognate codons, terms that have long been used but not well understood. The team determined the differences between the two at both the molecular and mechanistic levels, and developed a simple drug-based test to differentiate them.


Messenger RNA tells the ribosome what kind of proteins to make and how much. Codons are the three-part packets of information in DNA that specify which amino acids should end up in the protein.


Corresponding packets in aminoacyl transfer RNAs (aa-tRNA), called anticodons, read them. If the wrong codon is selected, the wrong amino acid ends up in the protein, which can alter or destroy the function of that protein and cause human disease, says Dr. Dinman.
Using firefly luciferase the team discovered that the difference between near- and non-cognate aa-tRNAs lies in the potential of near-cognate aa-tRNAs to pair up with messenger RNA at all three positions to create three sets of base pairs. This serves as the signal to tell the ribosome to use that aa-tRNA. In contrast, that potential does not exist between mRNAs and non-cognate aa-tRNAs. Some drugs may be best suited for making the ribosomes use near-cognate aa-tRNAs, while others work another way and are best used for non-cognate cases. The nature of the mutation responsible for a specific disease, whether it is near- or non-cognate, will determine the therapeutic strategy, according to Dr. Dinman.


Source: www.bio.com

Researchers reveal structure of protein altered in autism

A research team led by scientists from Skaggs School of Pharmacy and Pharmaceutical Sciences, the University of California San Diego (UCSD) in the United States, has discovered how certain genetic mutations affect the protein complex involved in autism spectrum disorders and contribute to the developmental abnormalities found in children with autism. Their work involving mapping the structure of the implicated protein complex should help scientists pinpoint the consequences of other genetic abnormalities associated with autism. First author Dr. Davide Comoletti said that researchers could now make predictions about how mutations in the gene affect the structure of the gene product.


Dr. Comoletti and colleagues studied the neuroligin family of proteins that are encoded by genes known to be mutated in some patients with autism. The neuroligins, and their partner proteins, the neurexins, are involved in the junctions (synapses) through which cells of the nervous system signal to one another and to non-neuronal tissues such as muscle. These structural studies on neuroligins and neurexins are a major step towards defining the synaptic organization at the molecular level.


Normally, individual neuroligins are encoded to interact with specific neurexin partners in neurotransmission. Incorrect partnering, which results when a mutant neuroligin fails to properly align at synapses, helps explain why autism spectrum disorders are manifested in subtle behavioural abnormalities that are seen at an early age. Abnormal synaptic development in nerve connections is likely to lead to cognitive deficits observed in patients with autism.


Source: www.eurekalert.org

AGRI BIOTECH

Tomato with floral, fruity flavour

Israeli researchers, led by Dr. Efraim Lewinsohn of Newe Yaar Research, say they have genetically engineered tomatoes to give hints of lemon and rose aromas. The transgenic tomato includes a gene from a variety of lemon basil, Ocimum basilicum, that produces geraniol synthase, an aroma-making enzyme.


A panel of 82 people tested the genetically modified (GM) fruit against unmodified counterparts. Nearly everyone detected the novel aromas, which the testers described as perfume, rose, geranium and lemon grass. In terms of taste, close to 60 per cent preferred the GM tomatoes. A potential drawback is that the GM tomato has only a light red colour, as they have only half as much lycopene as normal tomatoes. Lycopene is an antioxidant, a compound credited with health-giving qualities. However, offsetting the low levels of lycopene are higher levels of compounds called volatile terpenoids, which have anti-microbial, anti-fungal and pesticidal qualities. The GM tomato, therefore, may have longer shelf life and need less pesticide to grow, Dr. Lewinsohn contends.


Source: www.abc.net.au

Rice engineered to carry cholera vaccine

A team of Japanese researchers, led by Dr. Hiroshi Kiyono of the division of mucosal immunology at the University of Tokyo, has developed a type of rice that can carry a vaccine for cholera. A major advantage of this approach, the team said, it that it causes immune reactions both system-wide in the body and in mucosal tissues such as in the mouth, nose and genital tract. Standard injected vaccines do not spur immune responses in the mucosal areas. That means the new vaccine may an advantage against pathogens that typically infect these membranes, such as Escherichia coli, cholera, human immunodeficiency virus (HIV), influenza virus and the SARS virus.


Attempts to alter plants to produce proteins that induce an immune reaction to various diseases have been under way for years, but none has reached the stage for human use. While rice is only the latest of several plants being tested as potential means of producing vaccines, the development is important to medically underserved countries that lack refrigeration to store regular vaccines.


The work is still preliminary, having been tested only in mice. The Japanese researchers were reportedly able to generate a protective immune response in the mice while avoiding any allergic reaction to the rice itself. The use of rice engineered to produce a vaccine reaction does not mean it is an edible vaccine, Dr. Kiyono stressed. Instead, the vaccine is delivered in a capsule or pill containing rice powder, just like a drug.


Source: www.sci-tech-today.com

Maize resistant to streak virus

In South Africa, scientists at the University of Cape Town and Pannar Pty. Ltd., a seed company, have reportedly developed a resistant variety of maize that could alleviate food shortages in Africa. The maize variety resistant to maize streak viruses (MSV) is the first genetically engineered crop developed and tested solely by Africans.
MSV are Gemini-viruses that can destroy most of a maize crop, said Dr. Dionne Shepherd of the University of Cape Town, a member of the team of researchers. They are endemic to sub-Saharan Africa and adjacent Indian Ocean islands where they are transmitted by leafhoppers.


The resistance to MSV requires multiple genes located on different chromosomes, thus ruling out a straightforward process. The researchers mutated a viral gene, which encodes a protein that MSV needs to replicate itself, and inserted it into maize plants. When the virus infects one of these transgenic maize plants, the mutated protein, which is expressed at a high level, prevents the virus from replicating and killing the plant.


The transgenic maize variety has proven consistently resistant to MSV and the trait can reliably be passed on to the next generation and in crosses to other varieties, the researchers stated. Field trials are scheduled to begin soon, to test the effectiveness of the technology in the field as well as to ensure that the variety has no unintended effects on beneficial organisms that may feed on it. The resistant maize variety will also be tested to ensure that the viral protein is digestible and non-allergenic.


Source: www.agbios.com

The key to orange cauliflower

Orange cauliflower, first discovered in a farmers white cauliflower field in Canada about 30 years ago, has distinct nutritional advantages. Now, scientists at Cornell University, the United States, have identified the genetic mutation behind the unusual orange hue. The finding may lead to more nutritious staple crops, including maize, potato, rice, sorghum and wheat.


Some crops have the ability to synthesize beta-carotene, a precursor to the essential nutrient vitamin A, but the ability is often limited because they lack a metabolic sink a place to store the compound. The gene mutation, isolated by Cornell plant geneticist Dr. Li Li and colleagues, allows the vegetable to hold more beta-carotene, responsible for the orange colour.


Other researchers have created golden rice by inserting several genes that increases the synthesis of beta-carotene. But this technique has proved less effective in many plants. Dr. Lis new research, which increases a plants ability to store beta-carotene, may offer an alternative and complementary technique for making staple crops more nutritious.


Source: www.checkbiotech.com

Nanotech gateway to plant cells

A team of plant scientists and materials chemists at the Iowa State University (ISU), the United States, have successfully used nanotechnology to penetrate plant cell walls and simultaneously deliver a gene and a chemical that triggers its expression with controlled precision. Their breakthrough brings nanotechnology to agricultural biotechnology and plant biology, creating a powerful new tool for targeted delivery into plant cells.


Currently, scientists can successfully introduce a gene into a plant cell. In a separate process, chemicals are used to activate the genes function. The process is imprecise and the chemicals could be toxic to the plant. Using the mesoporous silica nanoparticles, two biogenic species can be delivered at the same time. We can bring in a gene and induce it in a controlled manner at the same time and at the same location. That has never been done before, said Dr. Kan Wang, professor of agronomy and director of the Centre for Plant Transformation.


The ISU team bagan with an Iowa State University proprietary technology a porous, silica nanoparticle system. Spherical in shape, the particles have arrays of independent porous channels. The channels form a honeycomb-like structure that can be filled with chemicals or molecules. One gram of this kind of material can have a total surface area of a football field, making it possible to carry a large payload, say the researchers. The nanoparticle has a capping strategy that seals the chemical goods inside. The caps can be chemically activated to pop open and release the cargo inside animal cells. This unique feature provides total control for timing the delivery.


The chemists synthesized even smaller gold particles to cap the nanoparticles, so as to introduce the nanoparticles into walled plant cells using a gene gun. These golden gates not only prevent chemical leakage, but also add weight to the nanoparticles, enabling their delivery into the plant cell with the standard gene gun. The biologists then successfully used the technology to introduce DNA and chemicals to Arabidopsis, tobacco and corn plants.


Source: www.eurekalert.org

Herbicide-resistant GM soybean

The Brazilian Agropecuary Research Enterprise (Embrapa), together with BASF, has developed Brazils first genetically modified soybean for commercial purposes. The transgenic soybean has a gene of thale cress (Arabidopsis thaliana). The gene provides the soybean with resistance to imidazolinone herbicide.


The partnership of the two companies started in 1997, with BASF providing the gene patent and Embrapa developing the technology for genetic modification. According to Embrapa, several bio-security tests are being carried out to check the plants impact on the environment and human feeding. The results will be sent to the National Bio-security Technical Committee tasked to authorize such projects. The new soybean is expected to take over up to 20 per cent of the Brazilian market and will enhance BASFs competition with Monsanto.


Source: www.checkbiotech.org

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Biotech 2007 Life Sciences: A Global Transformation

Biotech 2007 focuses on the emergence of biotechnology as a global industry. This publication provides an overview of the latest developments and trends in biotech around the world along with detailed analysis on the progress and prospects for each nation reviewed. Biotech 2007 provides: special features on emerging players such as China, India, Japan and Singapore; interviews with biotech leaders; industry financials for 2006; an analysis of key activities taking place in the industry sectors; and industry highlights including new product approvals, advances in technology, scientific activity, as well as a thorough analysis of the venture capital environment and capital markets.


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