Chemical Education Today
Reports from Other Journals
Research Advances by Angela G. King
In a Crisis, Creating DNA Vaccine Could Help Save Lives, Slow Spread of “Bird Flu” Researchers scrambling to combat a virulent form of avian influenza (“bird flu”)—avian influenza A (H5N1) virus— that could mutate into a form easily spread among humans should consider developing vaccines based on DNA, according to British biochemical engineers. DNA vaccines, they say, can be produced more rapidly than conventional vaccines and could possibly save thousands of lives if a global influenza outbreak occurs. A DNA-based vaccine could be a potent weapon against this emerging threat, particularly if enough conventional vaccine isn’t available, according to Peter Dunnill and his colleagues at University College London. However, they caution that any DNA vaccine should only be used as needed to slow the spread of the disease because the technique is largely untested in humans. This analysis appears in the November–December issue of the journal Biotechnology Progress, a co-publication of the American Chemical Society and the American Institutes of Chemical Engineers. The avian influenza A (H5N1) virus has spread among birds throughout Southeast Asia and has been recently detected in Eastern Europe. The virus has killed more than 60 people in Asia since 2003 and forced the slaughter of millions of birds. There are no confirmed cases of human-to-human transmission of this flu, although that could change as the virus continues to mutate, Dunnill says. If that occurs, current production facilities are unlikely to meet global demands for conventional vaccines in time to avert a pandemic, Dunnill says. However, it might be possible to quickly produce a DNA vaccine by adapting the manufacturing processes of selected biopharmaceutical and antibiotic plants in countries such as the United States, China, and India. “A DNA vaccine is not a panacea, however it could be useful if the situation
Figure 1. Alternative processing routes for DNA vaccine production. Reprinted with permission from Biotechnol. Prog. 2005, 21, 1577–1592. Copyright 2006 American Chemical Society and American Institute of Chemical Engineers.
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Reports from Other Journals gets out of hand”, Dunnill says. “But if we’re going to try it, we need to move. You can’t expect to walk into a production facility, hand over the instructions, and expect them to make it on the spot. It’s going to take some weeks, and we really don’t know how much time we have.” A DNA vaccine could be produced in as little as two or three weeks, Dunnill says. To do it, scientists would create a “loop” of DNA that contains the construction plans for a protein on the outer surface of the H5N1 virus. When that DNA is injected into cells, it would quickly reproduce the protein and trigger immunization in much the same way as a conventional vaccine. In contrast, producing conventional vaccines from viruses incubated in fertilized eggs can take up to six months, which is too long to effectively prevent an influenza pandemic, Dunnill says. Although no commercial influenza DNA vaccine is currently available, these vaccines have worked well in animals. However, human trials are still in the early stages so the safety and efficacy of these vaccines isn’t fully established in people. But these trials could be accelerated, Dunnill says, particularly if the H5N1 virus eventually causes large numbers of human deaths and outpaces the supply of conventional vaccine. In the worst case scenario, he suggests, using a DNA vaccine could be a “stop-gap” measure until enough conventional vaccine is available to corral the pandemic.
More Information 1. Hoare, M.; Levy, M. S.; Bracewell, D. G.; Doig, S. D.; Kong, S.; Titchener-Hooker, N.; Ward, J. M.; Dunnill, P. Bioprocess Engineering Issues That Would Be Faced in Producing a DNA Vaccine at up to 100 m3 Fermentation Scale for an Influenza Pandemic. Biotechnol. Prog. 2005, 21, 1577–1592. 2. This Journal has previously published an undergraduate lab experiment of interest. See Jarrett, Ronald M. Simulating How a Virus Spreads through a Population: An Introduction to Acid–Base Chemistry in the Organic Chemistry Laboratory. J. Chem. Educ. 2001, 78, 525.
Gold Nanoparticles, Radiation Combo May Slow Alzheimer’s Chemists in Chile and Spain have identified a new approach for the possible treatment of Alzheimer’s disease that they say has the potential to destroy beta-amyloid fibrils and plaque—hypothesized to contribute to the mental decline of people with Alzheimer’s. The researchers say the new technique, which they call a type of “molecular surgery,” could halt or slow the disease’s progress without harming healthy brain cells. Using test tube studies, the scientists attached gold nanoparticles (AuNPs) to a group of beta-amyloid fibrils formed from A, a small protein involved in Alzheimer’s disease. The team then incubated the resulting mixture for several days and exposed it to weak microwave fields for several hours. The AuNPs were linked to a peptide (Cys-PEP) that selectively binds to A aggregates. The energy levels of the fields were six times smaller than those produced by conventional cell phones and unlikely to harm healthy cells, the researchers say. The fibrils subsequently dissolved and remained dissolved for at least one 524
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week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers. The dissolution could be monitored by color changes: the reddish color of dispersed AuNP–CysPEP disappeared as the conjugate bound to the growing fibrils, only to return after irradiation. Transmission electron microscopy was used to characterize the morphology of aggregates both before and after microwave irradiation. Before irradiation, fibrils with profuse amounts of AuNPs attached were seen while there was virtually no isolated AuNP-CysPEP observed. After irradiation, there was a more diverse display of AuNP and fibril species. The same approach also holds promise for treating other neurodegenerative diseases that involve protein aggregation, including Parkinson’s and Huntington’s diseases, says study leader Marcelo J. Kogan, of the University of Chile in Santiago. He says that the approach is similar to that of another experimental technique that uses metallic nanoparticles to label and destroy cancer cells. Animal studies are planned, Kogan says. There’s currently no cure for Alzheimer’s disease and no one is sure of its exact causes. The disease affects an estimated 4.5 million people in the U.S., according to the National Institute on Aging. That figure is expected to rise dramatically as the population ages, experts predict.
More Information 1. Kogan, Marcelo J.; Bastus, Neus G.; Amigo, Roger; GrilloBosch, Dolors; Araya, Eyleen; Turiel, Antonio; Labarta, Amilcar; Giralt, Ernest; Puntes, Victor F. NanoparticleMediated Local and Remote Manipulation of Protein Aggregation. Nano Letters 2006, 6, 110–115. 2. More information from the National Institute on Aging is available on the Web. See http://www.nia.nih.gov/ (accessed Feb 2006). 3. This Journal has previously reported an experiment in which students prepare gold nanoparticles. See Dungey, Keenan E.; Muller, David P.; Gunter, Tammy. Preparation of Dppe-Stabilized Gold Nanoparticles. J. Chem. Educ. 2005, 82, 769. 4. This Journal has also published an account of various uses of microwave ovens in the chemistry lab. See Cresswell, Sarah L.; Haswell, Stephen J. Microwave Ovens—Out of the Kitchen. J. Chem. Educ. 2001, 78, 900–904. 5. This Journal has published a Classroom Activity in which students make gold nanoparticles. See McFarland, A. D.; Haynes, C. L.; Mirkin, C. A.; Van Duyne, R. P.; Godwin, H. A. J. Chem. Educ. 2004, 81, 544A.
New “Self-Exploding” Microcapsules Could Take Sting out of Drug Delivery Belgian chemists from Ghent University and the Université Catholique de Louvain have developed “self-exploding” microcapsules that could one day precisely release macromolecular drugs and vaccines inside the human body some weeks or even months after injection. Unlike some other microcapsules, which release their drug cargo only when exposed to ultrasonic waves or another external trigger, the new system relies on internal mechanisms to do
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Reports from Other Journals the same job. Each of the new microparticles features a biodegradable hydrogel core that is coated by a lipid membrane. As the gel biodegrades, pressure builds up in the membrane. Eventually the membrane ruptures, releasing the medication. The team of researchers, led by Stefaan De Smedt, prepared dextran hydroxyethyl methacrylate (dex-HEMA) microgels and used electrostatic interactions to coat them with lipids. Dex-HEMA is biocompatible and dex-HEMA microgels afford protein encapsulation efficiencies as high as 90%. The scientists then demonstated that the degradation of the lipidcoated microogels caused swelling pressure increases, resulting in the rupture of the lipid membrane surrounding the degraded microgels. The degradation behavior of the microgels was followed with confocal laser scanning microscopy (CLSM). Degradation rates were accelerated with the addition of sodium hydroxide. This system, the researchers note, could change how some vaccines are administered. Instead of an initial injection followed by a series of boosters, for instance, certain vaccines could be given in a single shot with the “booster” microcapsules timed to rupture at appropriate intervals.
More Information 1. De Geest, Bruno G.; Stubbe, Barbara G.; Jonas, Alain M.; Van Thienen, Tinneke; Hinrichs, Wouter L. J.; Demeester, Joseph; De Smedt, Stefaan C. Self-Exploding Lipid-Coated Microgels. Biomacromolecules 2006, 7, 373–379. 2. De Geest, Bruno G.; Dejugnat, Christophe; Sukhorukov, Gleb B.; Braeckmans, Kevin; De Smedt, Stefaan C.; Demeester, Joseph. Self-Rupturing Microcapsules. Advanced Materials 2005, 17, 2357–2361. 3. An undergraduate experimental module on hydrogels has been published in this Journal. See Schueneman, Susan M.; Chen, Wei. Environmentally Responsive Hydrogels. J. Chem. Educ. 2002, 79, 860–862. 4. More information on CLSM, including an online simulator, is available at http://micro.magnet.fsu.edu/primer/techniques/confocal/ (accessed Jan 2006).
Angela G. King is Senior Lecturer in Chemistry at Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109;
[email protected].
Figure 2. CLSM snapshots of degrading dex-HEMA-MAA microgels coated with SOPC/DOTAP. Labels indicate the time after the addition of NaOH to the microgels. The lipids appear green while the microgels appear red. After explosion of the microgels (120 s) only lipid remnants can be observed. Reprinted with permission from Biomacromolecules 2006, 7, 373–379. Copyright 2006 American Chemical Society.
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