VATIS Update Biotechnology . May-Jun 2003

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Biotechnology May-Jun 2003

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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Critical early-defence trigger in plants found

A key to natural disease resistance in plants has been discovered by a team of biologists from the Boyce Thompson Institute for Plant Research and Cornell University, New York, the United States. The research describes the discovery of the gene that codes for an enzyme, which gets activated when a plant senses an attack by a pathogen. When activated, the enzyme produces nitric oxide (NO), a chemical that tells the plant to turn on its defence arsenal. By enhancing the activity of the enzyme, the natural ability for disease resistance in plants could be boosted without resorting to pesticides or the introduction of non-plant genes.

According to Dr. Daniel F. Klessig, the team leader, the discovery provides a new understanding of the biochemical and genetic pathways in plants that enable them to protect themselves from disease. It would now be possible to modify plants so that they produce NO faster, or in larger amounts, when they are attacked by a disease-causing pathogen, enabling better self-protection.

Genetic route to drought-resistant plants

Scientists at Purdue University, the United States, have cloned the gene WAX2, which is directly associated with the synthesis of the protective layer of plants, called the cuticle, and the waxes it contains. They discovered a fast-wilting mutant Arabidopsis, which when compared with a wild type (normal) plant had less ability to retain water. This is because the mutant, called wax2, has a different cuticle structure than found in a plant that has the normal gene, WAX2.

Dr. Matt Jenks and his research team isolated more than 20 mutant Arabidopsis plants that showed alterations in the amount of wax they produced. Of these, a few lost water more quickly than the wild type. The mutant wax2 was the most drought-susceptible. It was found that unlike previously described wax mutants, removal of the WAX2 gene product causes dramatic alteration in the cuticle membrane and the plant is no longer able to prevent water loss. When the cuticle membrane structure is changed because of the wax2 malfunction of the WAX2 gene, the protective wax within the cuticle membrane is displaced, affecting transpiration that helps plants emit waste matter. The plant becomes very permeable to water and is less able to withstand drought conditions. It is hoped that through this study, it would be possible to modify economically important crops to grow better during drought. 


Tobacco plant used to produce antibodies

Scientists led by Dr. Hilary Koprowski of the Biotechnology Foundation at the Jefferson Medical College, Philadelphia, the United States, have genetically engineered tobacco plants to produce human protein antibodies against rabies. They inserted DNA coding for an antibody against the rabies virus into tobacco plants, which, in turn, became factories churning out the antibody. The researchers first showed that the plant-derived antibody could neutralize rabies virus and prevent infection in mice, which were inoculated with a lethal dose of the street virus. According to Dr. Koprowski, the antibody produced in tobacco is as good as the one produced in animal cells and should be safer and less expensive to produce. 


Rice chromosome has twice the genes expected

In the United States, a team of scientists led by Dr. Robin Buell of the Institute for Genomic Research and Dr. Rod A. Wing of the University of Arizona has sequenced the smallest rice chromosome and found that it has nearly twice as many genes as the draft DNA sequence had predicted. The new finished sequence and analysis of rice Chromosome 10 confirms that the rice genome is closely similar to that of other grains, particularly sorghum and maize. It also offers a close look at the compacted short arm of the chromosome, which is a gene-poor heterochromatic region of the rice genome. The finished Chromosome 10 sequence which helped researchers identify about 1,700 additional rice genes shows the importance of completing a draft DNA sequence. The positional information fleshes out the earlier draft sequences that discovered only half of the genes on Chromosome 10, and with this the scientists have moved closer to the goal of improving a crop that feeds much of the world. The new study predicts about 3,500 genes on Chromosome 10, which encompasses about 22 million DNA base pairs. The previous estimate, based on the draft genome blueprint, had predicted about half that number of genes. The finished genome still has seven gaps, representing about 4 per cent of the total chromosome sequence. The final finished rice genome sequence is expected by 2004.


India to develop detection protocol for GM food

The Department of Biotechnology, Government of India, is working on developing a detection kit for transgenic food products. Although the Indian Environmental Protection Act 1986 and the Rules 1989 specify the protocol for experimentation and commercial production of GM products, there was a need for taking strict measures on approval of food to ensure safety. There could be restrictions to market such products, and transgenic products would need to be specifically labelled to distinguish them from traditional products. If the experimental works going on at a couple of Indian institutes turn fruitful and the government finds the products safe, the country will witness the launch of genetically modified food in the near future. In the pipeline are GM rice, wheat, potato and tomato, with transgenic potato in the race to hit the field first. GM food could very well replace nutraceuticals and redefine the whole concept of food supplements. Work on edible vaccines is also progressing at Indian institutes as part of DBT-funded projects, indicating that in the long-term future vegetables and fruits would replace medicine. 

Express Pharma Pulse, 24 April 2003


Anthrax genome decoded 

A team of researchers at the Institute of Genomic Research, Madison, the United States, has completed the genetic blueprint of Bacillus anthracis. The cause of potentially fatal inhalational anthrax, B. anthracis differs very little from the common soil bacterium that is its near relative, the scientists have discovered. Those minor genetic differences, however, give B. anthracis its disease-causing properties and may also give scientists valuable clues to its vulnerabilities. The complete sequence of the 5.2 million base pairs of the DNA in B. anthracis single chromosome has been published. 

The scientists compared an isolate of the Ames strain of B. anthracis with two closely related Bacillus bacteria, and found little difference among these genomes. They also found a number of genes encoding proteins, which B. anthracis may need to enter its hosts cells and could provide targets for drugs designed against the organism. Further, unlike its near relatives, B. anthracis has genes that give it the ability to thrive on protein-rich matter such as the decaying animal bodies it frequently grows on. It also has an enhanced capacity to scavenge iron, which it may use to survive in its host. Using techniques of comparative genomics, the scientists evaluated several clues about the possible evolutionary pathway taken by B. anthracis ancestors. The similarities between certain B. anthracis genes and those of microbes that infect insects, for instance, suggest infection of insects by a recent ancestor of B. anthracis. 


Twice as many genes in the human genome

Researchers at Yale University, New York, the United States, have provided preliminary evidence that there may be more than twice as many genes in the human genome than previously predicted. Using an advanced genomic technique, they looked for all the genes on human chromosome 22 the most well studied human chromosome and found that many of the known, related and predicted genes were verified to be expressed in the cell. More importantly, the study revealed twice as many transcribed bases than have been reported previously, potentially indicating that there are twice as many genes in the human genome. This is the next and necessary step in analysing and understanding the human genome.

The scientists mapped all the coding regions of chromosome 22 using an advanced microarray technology. They found that a DNA microarray representing nearly all of the unique sequences of human chromosome 22 was constructed and used to measure global transcriptional activity in a complex tissue similar to the placenta. A significant fraction of these novel fragments can be found in the mouse genome, further indicating their biological relevance. This study was a proof of the principle that it was possible to find all the regions of a chromosome that are biologically relevant and could be used to study the entire human genome. 


Research identifies genes associated with asthma 

An international group of researchers led by scientists at Cincinnati Childrens Hospital Medical Centre, Cincinnati, the United States, have discovered 291 genes associated with asthma. This discovery is being hailed as one of the most significant breakthroughs in allergic diseases research in recent years. Prior to this study, it was thought that only a dozen or so genes were implicated in asthma. The discovery that asthma involves the interplay of 291 genes has tremendous therapeutic and diagnostic implications. According to Dr. Marc Rothenberg, Director of Allergy and Immunology at Cincinnati Childrens Hospital Medical Centre, although each gene may represent a target for drug development, one gene in particular, arginase, regulates pathways that are critical in an asthmatic reaction. As arginase is involved regardless of the specific allergen, a treatment for asthma could be devised by targeting arginase. 

The study which involved scientists in Australia, Canada and the United States capitalized on both the human and mouse genome projects. It used lung tissue from mice with experimental models of asthma induced by different allergens. After analysing the tissue with DNA microarrays, also known as gene chips, they discovered that the expression of 6.5 per cent of the mouse genome was altered in an asthmatic lung. The study identified multiple new pathways involved in asthma. One such process involved the cellular machinery that processes arginine, an amino acid normally consumed in the diet. Once processed in the body, arginine can be used to synthesise critical molecules such as growth factors, connective tissue proteins and nitric oxide. 

In particular, the arginine transporter protein and the enzymes that act on it, arginase I and arginase II, were found to play an important role. The researchers found that the breakdown of arginine is shifted away from its normal pathway during asthma owing to production of arginase. They then compared these mouse DNA results with samples of asthmatic human lung tissue and found that the arginase pathway was critical in human disease. According to the researchers, because arginase is upstream in regulating pathways that are critical in allergic reactions, blocking the arginase pathway may benefit patients regardless of which gene is implicated in their asthma. 


Unravelling HIVs complex family history

Scientists at the University of Nottingham, the United Kingdom, have discovered that the parent of the HIV virus was the product of a union between two viruses that affect monkeys. This genetic mixing occurred in a chimpanzee at least one million years ago, although it is thought that HIV did not cross into humans until the 1930s. 

The complex genetic history of HIV viruses came to light when researchers tried to construct family trees connecting the different genomic elements in the viruses. If the viruses shared the same genetic history, then these trees would match up. According to Dr. Paul Sharp of the University of Nottingham trees stemming from different parts of the genome put the virus in different places. The Simian Immunodeficiency Virus (SIV) found in chimps, and which led to the most widespread human strain HIV-1, has elements of two other SIVs. These strains are found in red-capped mangabeys and greater spot-nosed monkeys, but it was not clear which of the SIV strains were the originals.

Now Dr. Sharp and his team have constructed several family trees based on different assumptions about the order in which genetic mutations occurred during the evolution of the viruses. These indicate that the chimp SIV is the product of gene swapping between the monkey viruses. Chimps, which are known to hunt a variety of monkeys, probably became infected with both the SIV strains by eating the flesh of monkeys. They could then have swapped genetic material and produced the virus that eventually crossed into humans.

It is believed that the gene mixing happened at least a million years ago because the chimp SIV virus is present in two sub-species of chimpanzee that diverged at that time. The finding raises the possibility that chimps are infected with other combination viruses that could be dangerous to humans. 


Researchers identify new colon cancer genes

A team of scientists led by Dr. Best Vogelstein of the Howard Hughes Medical Institute (HHMI), the United States, have identified new gene mutations that occur in a significant fraction of colon cancers. It is known that abnormal activity of tyrosine kinases can hasten the development of certain forms of cancer. Kinases are important enzymes that activate other proteins by adding a phosphate group to them. In this first-of-a-kind survey, researchers analysed a catalogue of all known tyrosine kinase enzymes to screen the genes that produce tyrosine kinases, reasoning that somewhere in this genomic landscape they might encounter novel mutations that spur colon cancer and other types of cancer.

The starting point for the studies was a detailed catalogue of all kinases in the cell, prepared by Dr. Tony Hunter and his colleagues at the Salk Institute for Biological Studies, California, the United States, and collaborators at the biotechnology company Sugen. According to Vogelstein, this catalogue, which its developer named the kinome, constitutes an ideal collection of targets for cancer researchers seeking to stop the uncontrolled proliferation of cancer cells and could help identify many of the genes responsible for common cancers, like colon cancer. 

Chronicle Pharmabiz, 15 May 2003



Novel bioinformatics software 

A novel software for simultaneous comparison of multiple proteomes has been developed at the G.N. Ramachandran Knowledge Centre for Genomic Informatics, at the Institute of Genomics and Integrative Biology, New Delhi, India. PLHOSTFA or Peptide Library-based Homology Search Tool [Functional Assignment] makes a proteome-wise comparison of several organisms simultaneously and reports longest invariant peptides present in minimum number of organisms as specified by the user. It provides a novel method for simultaneous comparison of multiple proteomes comprising millions of peptides and retrieves functional signatures without a priori classification of protein functional families. The web-based software is useful in the fields of training, R&D and drug development.

Chronicle Pharmabiz, 22 May 2003

CSIO develops DNA-based encryption with software

A new DNA-based encryption with software has been developed by the Central Scientific Instruments Organisation (CSIO), Chandigarh, India. This is useful in converting any text or picture into a DNA sequence and is being projected as a major step towards realizing molecular memory and storage devices. DNA is being used as an electronic device because it has the capability to sort information and decode information on demand to make the life go on within the individual and from generation to generation. DNA can use nanowire, which can be synthesized in any imaginable sequence of four bases (A,T,G,C). Using this property, CSIO is working on electrical characterization and change transport in DNA, which will have great impact on design of DNA-based electronics and understanding of life processes. 

Chronicle Pharmabiz, 1 May 2003

End-to-end bioinformatics software package from TCS

Tata Consultancy Services (TCS) of India has developed an end-to-end bioinformatics software package, called Biosuit, on Linux platform jointly with the Council for Scientific and Industrial Research and with support from the Department of Biotechnology, Government of India. The Alpha version of Biosuit will roll out in May 2003 with the full product expected to hit the market in one year.

Twenty leading academic bodies including the Indian Institute of Science, Institute of Genomics and Integrative Biology, Indian Institutes of Technology, Centre for DNA Fingerprinting and Diagnostics, and Universities of Hyderabad and Pune have contributed domain knowledge and tools for Biosuit. Biosuit would be comparable to Accedos, the best bioinformatics software available in the market, and at a lower, affordable price. 

Chronicle Pharmabiz, 24 April 2003

Soochika licensed to Singapore bioprocessing tech Institute

Strand Genomics Pvt. Ltd., Bangalore, India, has licensed Soochika, its microarray data mining and management product, to Singapore-based Bioprocessing Technology Institute under National University of Singapore. Soochika employs extensive data cleaning, filtering, transformation and normalization techniques. Soochika features three main analyses: pipelines-cluster analysis including multiple clustering techniques (like K-means, hierarchical, random walk, percolation, SOM, eigen-value based clustering, etc.), predictive model building (including supervised machine learning techniques like SVM, neural networks, decision tree analysis and linear regression) and differential analysis (including two-way tests, ANOVAs and other techniques). Its annotation module allows the user to get and organize relevant information on gene sequences for further analysis. This software runs on Windows, UNIX, Mac OS X and Linux platforms. 

Express Pharma Pulse, 22 May 2003


Toxin sensor chip combines electronics with living cell

Scientists at the University of California, Berkeley, the United States, have found a way to tap into the telltale electrical signals that mark cell death, to sound the alarm of a biochemical attack or test drug toxicity on human tissue. They used a microchip to electrically determine cell viability by detecting changes in the electrical resistance of a cell membrane within milliseconds after it is exposed to a toxic agent. They found that after a cell is exposed to a toxin, its electrical resistance experiences a quick spike before dropping dramatically when it dies, thereby making it possible to detect the viability of a cell directly and instantaneously. Scientists hope that this research would benefit those applications that rely upon the knowledge of whether a cell is alive or dead and has implications for use as a biochemical sensor. This device is based on micro-electromechanical single cell analysis technology and therefore lends itself to miniaturization. 

One of the properties of a dead cell is the breakage in membrane that would allow various ions to move through it and could be used to make a circuit that can be easily measured. This change in membrane permeability forms the basis for traditional cell viability assays that use colorimetric or fluorescent dyes. The molecules of the dye can only pass through the membrane of dead cells. Drug researchers investigating a chemicals toxicity to cancer cells, for example, would look to see whether the dead cells appeared fluorescent through a microscope. 

In this chip, a cell essentially lives in a nutrient-rich culture between two electrodes on a silicon wafer. The electrodes continuously probe the cell membrane, and track the amount of electrical current that is able to pass. The amount of cell membrane damage relates to the degree of ionic current, so that larger the damage, the greater the change in electrical resistance. Using electrical resistance to measure cell death is more efficient than dyes. Furthermore, the measurement takes a matter of milliseconds or seconds compared with half an hour or more that the traditional protocol requires. 


Human arteries grown from scratch

Scientists from Duke University Medical Centre, North Carolina, the United States, have grown human arteries from scratch. The technique could help produce spare blood vessels for bypass surgery. Every year, across the world, several thousand patients with coronary heart disease have bypass operations to improve the blood supply to their hearts. Surgeons use vessels from other parts of the body to circumvent blockage. These grafts often get clogged again, and patients run out of useable replacements after several operations.

The new procedure could grow a stockpile of donor-matched arteries. The scientists so far have harvested four arteries, each 80 mm long and 3 mm cross. First, ordinary human muscle cells are induced to multiply. Then a gene called hTERT is added to make them live longer, followed by seeding the cells on a hose-shaped scaffold of a biodegradable polymer. After two months, the support dissolves leaving a dense, muscular, tubular structure. Living cells are then dropped inside the complete artificial artery. However, other scientists have cautioned over the adoption of this approach. According to them 90 per cent of human tumours contain hTERT and although the gene does not cause cancer by itself, it might encourage cells to continue to grow inside a vessel and block it. The prototype arteries also need to be tested in the lab to see whether they can withstand millions of cycles of the heart pumping. 


Nanodevice helps overcome gene therapy limitations

In the United States, scientists from Northwest University, Chicago, and Argonne National Laboratory, Illinois, have created a hybrid nanodevice composed of a scaffolding of titanium oxide nanocrystals attached with snippets of DNA. The device may one day be used to target defective genes that play a role in cancer, neurological diseases and other conditions. The titanium oxide nanocrystals, which are less than a few billionths of a metre in diameter, may provide the ideal means of overcoming current limitations of gene therapy, such as adverse relations to genetically modified viruses used to deliver genes into cells.

The research team showed that nanocomposites not only retain the individual physical and biological activity of titanium oxide and of DNA, but also possess the unique property of separating when exposed to light or X-rays. For example, researchers would attach to the titanium oxide scaffolding a strand of DNA that matches a defective gene within a cell and introduce the nanoparticle into the nucleus of the cell. There the DNA would bind with its evil twin DNA strand to form a double-helix molecule. The scientists would then expose the nanoparticle to light or X-rays, which would cut off the defective gene. The titanium oxide scaffolding is also amenable to attaching other molecules, such as navigational peptides or proteins that, like viral vectors, can help the nanoparticles home in on the cell nucleus. 


Non-invasive glucose sensor

At the University of Pittsburgh, Pennsylvania, the United States, researchers have developed a non-invasive method to measure the glucose level in bodily fluid a thin plastic sensor that changes colour based on the concentrations of glucose. The current method of testing glucose in diabetes patients is by drawing blood from a finger prick and is dependent on patient skill and compliance for regular testing. The researchers plan to embed the sensing material into contact lenses worn in the patients eyes. Patients will determine their glucose levels by looking into a compact mirror that has a colour chart to indicate glucose concentrations and then comparing the colour of the sensing material with the chart. Red indicates very low glucose concentrations, violet indicates very high glucose concentrations and green shows normal glucose level. The researchers are still determining the number of detectable gradations, but expect that it may be as high as those in finger stick meters. It is expected that the technology would be able to be incorporated into commercially available contact lenses that could be replaced weekly. 



NPL set to acquire biotech and drug companies

Nicholas Piramal Limited (NPL) based in Mumbai, India, is close to finalizing deals in excess of US$100 million in Europe and the United States to acquire a company each in the field of biotechnology and generic drugs. The deals, to be signed within a few months, could be in the form of either joint ventures or outright acquisitions. NPL was in talks with a listed top-10 generic drugs company in the United States and with companies in the biotech sector in both the United States and Europe. Like NPL, these companies are all focused in the area of diabetes, cancer and cardio-vascular diseases. Tie-up with these companies will allow NPL to shift a lot of the research and development to the centre in India, which can offer low-cost, high-quality services and would also help utilize its capacities better. 

The Financial Express, 12 May 2003

AP & Ventureast float Indias first dedicated biotech fund

In a 2:1 joint venture with Ventureast of the Venture Capital group, the Government of Andhra Pradesh, India, has launched a US$30 million (Rs 1,500 million) venture fund for exclusive support to biotech companies, with precedence to start-ups. The fund APIDC Venture Capital (APIDC-VCL) has already received a commitment of US$2 million (Rs 100 million) from the Life Insurance Corporation of India, in addition to another US$2 million from Andhra Bank. The fund is expected to reach financial closure in nine months. APIDC-VCL, the first dedicated venture fund for the biotech industry in India, is in discussions with some more insurance/financial institutions to close the fund. 

The fund has already received 41 proposals from biotech start-ups and entrepreneurial aspirants, out of which 14 have been short-listed. The APIDC-VCLs norm is to pick up 2-49 per cent equity in the companies it funds, maintaining a minimum funding size of US$200,000 and a maximum of 25 per cent of the total fund size. 

The Economic Times, 24 May 2003

Chiron to make India a hub for vaccine business

Chiron Vaccine, a unit of Chiron Corporation based in California, the United States, has announced its plans to make India a regional hub for vaccine business. The companys rabies vaccine manufacturing facility, located at Ankleshwar in Gujarat, will be a sourcing facility for Southeast Asian countries. The Ankleshwar facility, approved recently by the World Health Organisation, is the second one after Germany to produce rabies vaccines. The company is evaluating Southeast Asian countries for registering its rabies vaccine prior to introduction.

An estimated 60,000 deaths are attributed to rabies each year globally. Chiron currently has a six per cent share of the global vaccine market, with a 12 per cent market share in Europe but barely 2 per cent in the United States. The company would also continue distribution of its polio vaccine with Indian partners and international agencies like UNICEF. Chiron would also introduce in India some of the innovative vaccines for paediatric infectious disease like meningitis.

Express Pharma Pulse, 24 April 2003

Metahelix and ViaLactia in functional genomics alliance

Metahelix Life Sciences Pvt. Ltd., an agricultural biotechnology company based in Bangalore, India, has signed a four-year plant functional genomics research agreement with ViaLactia Biosciences (NZ) Limited, a dairy biotechnology company in New Zealand. The research programme will involve the functional validation of a large number of genes from pasture plants. ViaLactia has been running a functional genomics programme on ryegrass. Ryegrass, a pasture grass, has been the subject of limited selective breeding pressure and therefore is a relatively wild species that could have important abiotic stress-tolerant traits that rice and other cereals could greatly benefit from.

ViaLactia and Metahelix intend to use the knowledge from this programme to develop commercial rice varieties in India through its subsidiary firm, Dhaanya Seeds. The alliance also emphasizes the importance of experimental functional validation of genes derived from genome sequencing efforts. 


Abbott in marketing tie-up with Artus for SARS diagnostic test

Artus GmbH, based in Germany, has entered into a worldwide marketing and distribution agreement with Abbott Laboratories, the United States, for the first commercial test to detect a form of the coronavirus suspected of causing Severe Acute Respiratory Syndrome (SARS). This test was developed jointly by Artus in collaboration and the Bernhard-Nocht-Institute for Tropical Medicine in Hamburg, Germany. It was introduced by Artus in April 2003 in Asia and Europe and was provided to laboratories under the direction of the World Health Organisation (WHO) and other major clinical sites conducting studies on the SARS virus. The test is based on a highly sensitive polymerase chain reaction (PCR) technology, which directly detects the virus in patient samples and gives results in two hours. The initial results of different sample types (sputum, swabs, stool and tissue) from the WHO laboratories are promising.

Under the agreement, Artus will manufacture the test kit and, after necessary regulatory approvals, Abbott will market and distribute it initially for use on the Roche LightCycler thermal cycler system in the United States, Canada, Germany, the United Kingdom and Austria, thereby supplementing the existing distribution agreements of Artus. Later, the test will also be available on the Applied Biosystems ABI Prism 7000 Sequence Detection System for worldwide distribution. Abbott will assist Artus in submitting this test to the United States Food and Drug Administration (FDA) as early as possible. 

Chronicle Pharmabiz, 22 May 2003


Scientists discover key to malaria drug resistance 

Researchers from the United Kingdom and Thailand are claiming a significant breakthrough in the search for a permanent treatment for malaria, based on the identification of part of a key protein involved in increasing the resistance of the malaria parasite to drugs. Most widely known drugs against malaria block the activity of a protein known as DHTR, which is essential to the survival of the malaria parasite. Mutations in this protein reduce the effectiveness of these treatments, giving rise to drug resistance that has so far significantly hampered efforts to fight the disease. The scientists have revealed the crystal structure of normal and mutated versions of DHTR, showing that resistant enzymes have specific features, information about which could lead to the design of new drug against the disease, which kills one African child every 30 seconds. 


Genetic smart bomb knocks out hepatitis C

Scientists at the Ontario Cancer Institute, Toronto, Canada, have been able to selectively target and destroy human liver cells harbouring the hepatitis C virus, using a new gene therapy approach. About 200 million people worldwide are affected by hepatitis C. The two treatments for this debilitating liver disease alpha interferon and ribavarin can reduce the level of infection, but the virus usually comes back. The key is a genetically engineered suicide gene, delivered aboard a harmless virus, which is triggered only when it enters a hepatitis-infected cell.

The sientists identified a unique protease enzyme produced by the hepatitis C virus. It is known that some proteases in human cells trigger proteins to kick-start the process by which the cell commits suicide. The genetic code that allows the proteins to recognize the human protease was removed and replaced with code specific to the hepatitis C protease. The DNA for the modified protein was then entered into cells using a harmless adenovirus. The researchers found that the viral protease caused an infected cell to order its own demise. 

The therapy successfully cleared low and medium-level hepatitis C infections in mice with implanted infected human liver cells. In mice with high levels of infection, the gene therapy slashed levels of the virus by a factor of 1,000. Importantly, the virus did not rebound after the gene therapy, as it can do with existing treatments. This is true for at least 28 days after gene therapy. The scientists are now doing further work to see this effect lasts longer. 


Bharat Biotech launches new generation typhoid vaccine 

TYPBAR, a highly purified ViCapsular polysaccharide typhoid vaccine, has been launched in India by its manufacturer Bharat Biotech International Ltd., Hyderabad. There are about 6-8 million cases of typhoid reported per year in India, and globally the number is around 16 million. The new generation vaccine is a single-dose primary immunization with higher seroprotection percentages and safety. It has been manufactured as per World Health Organisation (WHO) requirements of biological substance No. 48, conforming to the United States Food and Drug Administration (FDA) norms. 

The vaccine strain Salmonella typhi Ty2 for T1 of BAR was made available by Dr. John Robbins of the National Institute of Health in the United States, acclaimed as the father of polysaccharide vaccines. The company has planned for annual production of 50 million doses of TYPBAR and aims to tap a larger share of the market through its nation-wide marketing network and conducting massive public awareness campaigns. 

Express Pharma Pulse, 15 May 2003

Malaria vaccine gets a boost

In a major step towards an effective vaccine for malaria, scientists at the University of Oxford, the United Kingdom, have shown that by injecting humans with one scrap of DNA and then another in a poxvirus, their immune systems could be tricked into producing enough cells to attack malaria. Such drug double-acts which are being tested also against HIV, tuberculosis and some cancers are called heterologous prime-boost vaccinations.
Normal vaccines encourage part of the immune system to produce antibodies that smother free-living pathogens and instruct other immune cells to kill them. However, the pathogens that cause malaria, AIDS and tuberculosis dwell inside cells, safe from antibodies and conventional vaccines. Being malfunctioning human cells, cancer tumours are essentially the same. Only T-cells of the immune system can destroy such defective cells. The body produces tiny numbers of T-cells when immunized with harmless viruses containing short fragments of the DNA of the disease-causing organism.

The initial vaccination with DNA from the malaria parasite Plasmodium falciparum, followed by a dose of a benign virus containing different malaria DNA produces five to ten times more anti-malaria T-cells. It remains to be seen how effective the prime-boost vaccine is against real malaria infection, and malaria vaccines may ultimately consist of a mixture of prime-boost and other technologies. 


Protein complex helps bacteria resist antibiotics

In the United States, scientists from Lawrence Berkeley National Laboratory and the University of California at Berkeley, both in California, have used high-resolution images of a protein complex found in bacteria to show how bacteria survive attacks from different antibiotics. A growing health problem called multi-drug resistance, this robust defence is rooted in the protein complexs remarkable ability to capture and pump out a spectrum of structurally diverse compounds. The research may lead to the development of antibiotics that either evade or inhibit these pumps, allowing drugs to slip inside bacteria cells and kill them. The team studied AcrB, a protein that resides in the inner membrane of Escherichia coli cells and works in unison with two other proteins to rid the bacteria of toxins. Earlier research had shown that AcrB boasts a large cavity capable of binding with a vast range of antibiotics and other molecules, but precisely how this cavity accommodates so many shapes and sizes remained unclear.

The scientists crystallized the protein in the presence of four molecules an antibiotic, a dye, a disinfectant and a DNA binding molecule and then exposed the crystal to extremely bright X-rays that reveal the proteins molecular structure, including how the four molecules bind to the cavity. The resulting images portrayed a hungry, indiscriminate binding site. Each molecule bound to different locations in the cavity, and each bond utilized a different set of amino acid residues with room for many more types of interactions. The 3.5-3.8 angstrom resolution images provide the closest look yet of a phenomenon common to all living cells: the ability to expel a diverse flotilla of toxins using one pump. 

In healthy people, these so-called multi-drug efflux pumps play important roles. A complex called P-glycoprotein, for example, prevents the entry of toxic molecules across the mucosal surface of the intestinal tract, as well as the blood-brain barrier; but when over-expressed, it makes cancer cells resistant to a wide range of chemotherapy drugs. Similarly, harmless E. coli colonies inhabit animal intestines. In this environment, scientists theorize, AcrBs chief function is to trap and pump out toxic bile salt. However, mutated forms of E. coli cause food poisoning and AcrB shields the bacteria from many more compounds in addition to bile salt, which explains why a broad regimen of antibiotics is needed to fight the infection. It is suspected that the proteins cavity possesses areas where many types of antibiotics could be captured. This research also underscores the need to pursue alternative ways to fighting drug resistance. 

Express Pharma Pulse, 22 May 2003

Common gene variant linked to atherosclerosis

A common gene variant has been identified as a potent risk factor for early-onset atherosclerosis, according to scientists at the John Hopkins University, the United States. Atherosclerosis, the hardening of the arteries, is a key risk factor for heart attack and stroke. Using data and samples from two earlier studies of people at high risk for heart disease, the team found that those with at least one copy of a specific version of this gene, called klotho, are almost twice as likely to have undetected atherosclerosis than others. Smokers with low amounts of good cholesterol had 10-fold greater risk if they also had this gene variant.
Everyone has two copies of the klotho gene (one inherited from each parent). The researchers found that, of several common versions of klotho, one was associated with earlier death from all causes. They showed that approximately 2.5 per cent of the population has two copies of this bad version, known as KL-VS, while another 25 per cent carry one bad copy. While KL-VS may increase the risk of dying early, this new study suggests that it is possible to modify that risk by making lifestyle changes, which makes the possibility of genetic testing worth considering. 

The scientists determined that KL-VS was more common in people who die before the age of 65. Searching for an explanation of how klotho could reduce life expectancy, the researchers turned to two Hopkins studies originally designed to check for undetected atherosclerosis in apparently healthy siblings of people hospitalized for cardiovascular disease before the age of 60. More than 900 people between the ages of 39 and 59 were included in the new analysis. The scientist determined which klotho variant each participant had, and linked that to the persons clinical diagnosis and risk factors, which had been gathered as part of the older studies. 

Express Pharma Pulse, 15 May 2003

Scientists find new clues on how HIV evades antibodies

Scientists at the Howard Hughes Medical Institute and the University of Alabama, both in the United States, have found a new way in which the virus that causes AIDS manages to evade the bodys immune system. HIV infects immune system cells and impairs their function, leaving patients vulnerable to other infections. Viruses usually vary the protein sequence, or epitope, of their outer envelope, preventing the immune systems antibodies from targeting it. The HIV virus uses different strategies to evade the human antibodies. The re-searchers showed that the virus has an additional mechanism by which it escapes antibodies, a mechanism that was not previously recognized.

The scientists found that the neutralizing of epitopes on the virus did not change but instead, other parts of the viral envelope mutated at a faster rate than the immune system can adapt. The research has also been employed in a new method to test for antibodies, which can be applied to developing a vaccine for the disease. 

Chemical Weekly, 15 April 2003


Palau ratification sets Biosafety Protocol for introduction

On 13 June 2003, Palau became the 50th country to ratify the Cartagena Biosafety Protocol. With this accession of Palau, the required number of 50 instruments of ratification, accession, approval or acceptance by states has now been reached for the first legally binding international agreement governing the movement of living modified organisms (LMOs) across national borders.

In accordance with its Article 37, the Biosafety Protocol will enter into force on 11 September 2003, on the 90th day after the date of deposit of the 50th instrument of ratification, acceptance, approval or accession. The Protocol, adopted by the member governments of the Convention on Biological Diversity (CBD) on 29 January 2000 after more than five years of negotiation, aims at ensuring adequate safety in the trans-boundary movement and use of LMOs resulting from modern biotechnology that may have adverse effects on the biological diversity and human health.

When the Cartagena Protocol comes into effect, certain provisions apply immediately. Countries shipping LMOs for intentional introduction into the environment will have to give prior notification of the first shipment to an importing country that is a party to the Protocol under what is referred to as the Advance Informed Agreement procedure. Sufficient information will have to be provided to enable importing countries make informed decisions. Member countries of the Protocol will also be required to use the Biosafety Clearing-House (BCH) to fulfil a number of specific obligations. The BCH is a largely Internet-based facility set up under the Protocol to ease communications and exchange of information between the Parties. Furthermore, all shipments containing LMOs for intentional introduction into the environment will be clearly identified as such in the accompanying documentation, which must specify the identity and characteristics of the specific LMOs contained in each shipment. 

Following the agreements entry into force, the decision-making bodies of all member countries of the Protocol will meet in the first quarter of 2004 in Kuala Lumpur, Malaysia to address topics related to the operation and implementation of the Protocol. 


Four centres picked for GM rice technology transfer

The Department of Biotechnology (DBT) of the Government of India has identified four centres in the country for transfer of the golden rice gene in established traditional rice varieties. Dr. Ingo Potrykus of the Swiss Federal Institute of Technology and Dr. Peter Beyer of the University of Freiburg, the inventors of the genetically modified rice, had under the Indo-Swiss collaborative programme on biotechnology (ISCB) given the right to DBT to supply the seeds to research institutions, breeders and biotechnologists to optimize the trade in many respects and eventually provide an area-specific rice line for the peoples. Besides India, five other countries Viet Nam, China, South Africa, Indonesia and the Philippines have also been brought in under this programme for transfer of the golden rice technology in their respective traditional varieties.

In India, the Tamil Nadu Agricultural University is among the identified research institutes for transfer of this technology. Golden rice does not contain any new gene that was not there in rice or other species of plants. The transgenes in golden rice provided for synthetic ability for beta carotene in the endosperm, which was not there in normal rice. Ordinary rice, the staple food for a very large section of the world population, particularly in the developing countries, does not contain enough nutrients other than starch. Further, either out of ignorance or lack of accessibility, people do not take diverse items of foods. This had resulted in vitamin A deficiency, among others. Golden rice would help in getting some amount of pro-vitamin into the system without any additional effort. 

The Hindu Business Line, 23 May 2003

CCMB is centre of excellence

The Molecular and Cell Biology Network (MCBN) has chosen the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India, as a centre of excellence. MCBN is a Switzerland-based global network for molecular and cell biology. It works towards solving global problems like malnutrition, injurious environmental factors (chemical or physical in nature), uncontrolled population growth, degenerative diseases (such as cancer, immuno-deficiencies and ageing), the spreading of various infectious diseases, etc.

The network helps the scientists in the developing countries to share their common problems and develop the initiative and momentum to work in these fields. It assists the developing countries to develop the basic tools and techniques, and to establish a suitable environment for the development of solutions to problems employing molecular and cell biological approaches. UNESCO has been supporting MCBN for the last 12 years as part of its Basic Science Programme. 

Chronicle Pharmabiz, 10 April 2003

Ticel Biopark in Chennai to be functional by 2004

The Ticel Biopark in Chennai, India, is expected to be operational by January 2004. The Tamil Nadu Industrial Development Corporation (TIDCO) had entered into an MoU with the Cornell University of the United States in 2001 for setting up this TIDCO Centre of Life Sciences (Ticel) biotech park. The biotechnology park aims at providing the required support and exploiting the opportunities presented by the rich biodiversity in Tamil Nadu. With universities such as the Madras University Madurai Kamaraj University and Anna University, the state of Tamil Nadu also has skilled human resource.
The biotech park would include 18,000 square feet bio-resource centre with wet lab facilities and customized labs for the 120,000 square feet common tenancy area. Under the technical services agreement, Cornell will provide the design, technology and allied services for the park. It will also help in collaborative and contract research programmes, provide support and enable access to intellectual property at Cornells biotechnology park and elsewhere.

Chemical Weekly, 6 May 2003

Dolly lab to create virgin birth embryos

Dr. Ian Wilmut and colleagues at the Roslin Institute, Edinburgh, the United Kingdom the institute where Dolly the sheep was cloned have been granted the countrys first stem cell research licence allowing the creation of human embryos from unfertilized eggs. This process called parthenogenesis occurs naturally in some reptiles and insects, and allows females to reproduce without males, as their eggs are prompted to develop into embryos without being fertilized by sperms.

Dr. Wilmut and his team will artificially stimulate human egg cells to undergo parthenogenesis and then take stem cells from the resulting embryos. The aim is to develop the technology needed to maintain cell lines of human embryonic stem cells in the laboratory. It is hoped that this research would one day lead to treatments for diseases such as Parkinsons disease, heart disease and diabetes. The licence awarded to the Roslin team does not permit the embryonic stem cells obtained to be used for any therapeutic purpose, though they can be used to test new medicines. 


Malaysias biotech hub plans

As part of Malaysias initiative to become a developed nation by 2020, the countrys Prime Minister Mr. Mahathir Mohammad launched an ambitious plan to develop a biotechnology hub in the country. He has invited foreign scientists and investors to set up base at the BioValley project and to tap Malaysias rich biodiversity. The Malaysian Government would invest US$263 million (100 million ringgit) in the initial phase to build infrastructure and facilities including three research institutions dealing in genomics, pharmaceuticals and agriculture by 2006. The BioValley covers 2,000 acres in the Multimedia Super Corridor hi-tech zone, south of Kuala Lumpur. 

Chronicle Pharmabiz, 22 May 2003

Virus detectives seek source of SARS in Chinas wild animals

Workers and animals at the wild animal markets of southern China are now the focus of attention of researchers investigating the source of Severe Acute Respiratory Syndrome (SARS). The move follows reports that workers and animals at the markets show high rates of infection with coronaviruses, the family to which the virus believed to cause SARS belongs.

The possible link to wild animals emerged when a team from the University of Hong Kong revealed that a coronavirus resembling the SARS virus had been isolated from six masked palm civets (Paguma larvata) and a raccoon dog (Nyctereutes procyonoides) in a market in Shenzhen in Guangdong province. Antibodies against the virus were also found in a Chinese ferret badger (Melogale moschata) from the same market. Although the virus is not the same as that believed to cause SARS, five out of the ten civet handlers at the market had antibodies against the SARS virus in their blood. Results released by a Chinese government team show that 66 out of 508 animal handlers tested at the Guangdong markets had antibodies against the virus. This suggests that the virus could be jumping from wild animals to humans. Since the animal virus is similar to the SARS virus but different from other coronaviruses, it is now a prime suspect in the hunt for the origins of SARS. The likelihood that the virus is moving from humans to animals is, however, discounted by ongoing work, which suggests that the animal version has an extra stretch of 29 nucleotide bases. According to experts, viruses tend not to gain stretches of nucleotides when they jump across species. 


Indias first AIDS vaccine on trial

Indias first AIDS vaccine, developed by the Indian Council of Medical Research (ICMR), will be tested at the National AIDS Research Institute (NARI) in Pune. Currently, the vaccine is at the final stages of animal trials. The vaccine, Modified Vaccinia Ankara (MVA), would counter the strain of HIV sub-type C, which is the most prevalent in India. The decision to conduct trials at NARI follows a tripartite MoU signed between the Union Ministry of Health and Family Welfare, ICMR and International AIDS Vaccine Initiative (IAVI).

It is proposed to involve 40 healthy female and male volunteers in the age group of 15 to 50. The vector-based vaccine is administered thrice in one year to the volunteers. The immunization schedule would be 0, 4th and 6th months. Every volunteer would be monitored for 12 months to identify toxicity and immunogenicity, if any. If the person shows symptom of immunogenicity, he or she would be monitored for six more months. 

Chronicle Pharmabiz, 24 April 2003

JNU to set up knowledge park

The Jawaharlal Nehru University (JNU), New Delhi, India, is setting up a knowledge park on its campus to promote active interaction of its faculty and students with research and development arms of knowledge-based industries. JNU has expertise in the areas of information and biotechnology and a highly motivated student body, and it is felt that interaction between the university and industries in these areas can make a lasting impact on the growth of these industries in the country. 

JNU Knowledge park (JKP) will provide vast opportunities to JNU students in the form of internships and short-term employment. Space/laboratories created in the knowledge park will be leased out to frontline R&D companies in the areas of information technology, life sciences and biotechnology, social science, language, and emerging technologies such as robotics and nanotechnologies.JNU will provide land for the park on its campus. Support facilities like computer network, administrative support and crucial research infrastructure will be available in JKP, which will be under the administrative control of JNU and evolve as its integral part. While some seed money may be made available for JKP by the University Grants Commission, basic funding for establishing JKP is expected to come from non-UGC sources and innovative ideas will be explored to rope in funding for the knowledge park. 

BioSpectrum, March 2003

GM chickpea to be field-tested in 2004

Dr. Kiran Sharma and his colleagues at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) at Patancheru in Andhra Pradesh, India, have developed transgenic chickpeas to counter the legume pod borer Helicoverpa armigera and expects to carry out the first field-tests for the genetically modified chickpea in 2004. 

The transgenic chickpea has been developed using the Bt Cry1Ab gene. Insect bioassays with transgenics carrying this gene have started. The scientists are also engaged in developing transgenic chickpea with resistance to fungal pathogens and with tolerance to abiotic stresses such as drought and low temperature conditions. 



Cholera protein structure solved

Researchers at The Scripps Research Institute (TSRI), California, the United States, have solved structures of a bacterial protein called pilin, which is required for infection by pathogens that cause human diseases like meningitis, gonorrhoea, pneumonia, and cholera and other diarrhoeal diseases. A whole class of bacterial pathogens require the assembly of pilin into hair-like pilus filaments on their surface in order for them to attach to and infect host cells. The work directly focused on two pathogens Pseudomonas aeruginosa that causes severe lung infections in cystic fibrosis patients, AIDS patients and immuno-compromised individuals, and Vibrio cholerae that causes cholera, a potentially fatal diarrhoeal disease that primarily afflicts people in developing countries.

The pili are used by several types of bacteria to crawl around and stick to the intestine, lung and other mucosal surfaces, and to pick up foreign genes and DNA, bringing them aboard to increase the bacterias pathogenicity. In cholera, these pili are essential for the infection because they allow the bacteria to clump together and form a colony that protects them from the human immune response. This makes pili a good target for vaccine design, since blocking them should block the bacteriums ability to cause infection. The group first solved the structure of the individual pilin proteins from the V. cholerae bacterium using X- ray crystallography, in which crystals of molecules like proteins or DNA are made and then exposed to X-rays. The pattern of diffracted X-rays was collected and analysed to determine the structure of the molecules in the crystal.

The researchers then used electron microscopy to understand how pilin proteins were organized in the pilus filaments. X-ray crystallography and electron microscopy helped them build a model of the pili at the level of molecular detail. The structures provided new insights into how the pili group together and how they contribute to the pathogenesis of the bacteria, and furnished a unique molecular map of these proteins that should aid in the design of new vaccines and therapeutics. 


Two proteins at the heart of insulin response

Flaws in a two-protein combination of a molecular switch that responds to insulin has been shown to result in over-production of sugar in the liver an important feature of diabetes. Researchers led by Dr. Bruce Spiegelman at the Dana-Farber Cancer Institute at Boston, Massachusetts, the United States, have shown that drugs designed to block the interaction of the two switch proteins might be effective in treating diabetes, and with few side effects. They found that two previously known proteins in mice must dock, one on top of the other, to enable the switch to turn on genes that initiate the livers sugar-making process. When mutations damage one of the proteins, the switch cannot respond to insulin.
Gluconeogenesis, the livers manufacture of sugar from raw materials, is designed to provide the body (especially the brain) with necessary glucose when the person has been fasting and is not getting the sugar from food. Glucagon and glucocorticoid hormones initiate the process by sending signals to liver cells, triggering activity (DNA transcription) in genes that set gluconeogenesis in motion. Insulin has the opposite effect turning off gluconeogenesis when normal feeding resumes. Insulin activates the insulin receptors on liver cell surface, which send signals into the cell nuclei where they are received by the switch made up of the PGC-1alpha and FOXO1 proteins.
FOXO1 protein, known as a transcription factor, binds directly to the DNA molecules of the gluconeogenesis genes, causing them to transcribe into RNA. PGC-1alpha does not directly bind to the DNA, but docks onto the FOXO1 protein. In experiments with transgenic mice, it was shown that if a mutation occurs in the gene producing FOXO1, it results in an abnormal FOXO1 protein that is not sensitive to insulin. Consequently, the switch fails and the liver overproduces glucose. Dr. Spiegelman showed that the PGC-1alpha protein was the long-sought switch for gluconeogenesis, but how it worked with FOXO1 was not clear. This research suggests that blocking PGC-1alpha might be a new therapeutic strategy, and targeting just the combination of PGC-1alpha and FOXO1 would be a more finely pointed tool with fewer unwanted effects. 



Indian Biotech Industry: A Status Report 2003

The report discusses issues and throws light on the current status of this fledgling industry in India. The report contains profiles of nearly 400 biotech companies operating in India, besides an analytical review of the biotech industrys status with respect to the global scenario. Government initiatives, finance, problems, priorities, opportunities, strengths and weaknesses, segment-wise distribution, state-wise distribution, research status, etc. have also been addressed. The report has been prepared by Biotech Support Services (BSS), which has been active in providing informational support services through its website 

Contact: Biotech Support Services, 408, Archana Building, Sector-17, Vashi, Navi Mumbai 400 705, India.


B-147 The New Future of Biotechnology: Enabling Technologies and Star Products

The aim of this report is to provide a range of information from detailed market analyses through industry trends to quantify and qualify the impact of two leading technologies of the biotechnology industry genomics (including proteomics, pharmacogenomics and bioinformatics) and therapeutic antibodies. This report discusses two enabling technologies genomics and gene therapy as well as antibody products in an effort to define their impact on the medical industry. The report develops forecasts for genomics-based products, services and applications, gene therapy products, and antibody drugs for 1999, 2000 and 2005. It also contains comparative profiles of companies developing these enabling technologies and products. 

Contact: Business Communications Company, Inc., 25 Van Zant Street, Suit 13, Norwalk, Connecticut, 06855 1781, the United States. Tel: +1 (203) 853 4266, Fax: +1 (203) 853 0348.


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