Audio interview with Douglas Theobald of Brandeis University
Two Promising Candidate Drugs for Combating Hepatitis C Virus
Phase 1 clinical trials are under way for INX-189, a nucleotide polymerase inhibitor that is potently active in vitro against the hepatitis C virus (HCV), according to officials at Inhibitex of Alpharetta, Ga. INX-189 is licensed from the Welsh School of Pharmacy at Cardiff University in Cardiff, Wales, where it was first developed. Separately, Nicholas Meanwell at Bristol-Myers Squibb in Wallingford, Conn., and his collaborators say that their new candidate drug, designated BMS-790052, is "the most potent in vitro inhibitor" of HCV replication to date. It inhibits NS5A, a protein of HCV "with no known enzymatic function." When administered to HCV-infected subjects, a single 100-mg dose of BMS-790052 reduces viral load by nearly 3.5 orders of magnitude, they report. Details of their findings appear in the 6 May 2010 Nature (465:96-100). Worldwide, approximately 170 million people are infected with HCV, which can lead to liver cancer and cirrhosis, and is the leading cause of liver transplantation in western countries. HCV infections typically are treated with both ribavirin and interferon.
Ways to Make Working Strains of E. coli More Versatile, More Efficient
Notwithstanding other microbial species sharing its limelight, Escherichia coli remains a workhorse in genetic engineering circles. To optimize E. coli strains for making particular end products, a group of researchers in Korea developed a model that looks across the board at metabolic fluxes to identify gene amplification targets. This general approach, which they call flux scanning based on enforced objective flux, proved useful when evaluated for optimizing lycopene production, and was further enhanced when combined with specific gene knockouts, according to Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST in Daejeon, Republic of Korea, and collaborators. Details appear in the May 2010 Applied and Environmental Microbiology (76:3097-3105). Meanwhile, Justin Gallivan of Emory University in Atlanta, Ga., and his collaborators reprogrammed E. coli cells to migrate toward the herbicide atrazine. Another gene enables the engineered bacterial cells to degrade the herbicide. Details were published online in the 9 May 2010 Nature Chemical Biology (doi:10.1038/nchembio.369).
Noteworthy Gene Transfers involving Microbes, Parasites, Insects, Fish
Dogma to the contrary notwithstanding, pea aphids carry genes encoding enzymes that produce carotenoids, pigmented antioxidants that other animals cannot produce and thus acquire from their diets, according to Nancy Moran and Tyler Jarvik at the University of Arizona in Tucson. Moreover, according to their phylogenetic analyses, "these aphid genes are derived from fungal genes, which have been integrated into the [aphid] genome," they say. Aphids not only "are animals that make their own carotenoids," the insects apparently acquired that capacity via gene transfers. Details appear in the 30 April 2010 Science (328:624-627). Separately, an analysis of the genome of the lake sturgeon reveals that it contains trematode genes, according to Andrew DeWoody and Matthew C. Hale of Purdue University in West Lafayette, Indiana, and their collaborators. Thus, this fish species carries at least 15 genes that were acquired from Schistosoma, a parasitic worm-apparently a result of lateral gene transfer, they report in the April 2010 Genetica (138:745-756).
Federal Laws Tied to Drop in Research Efficiency Involving Ebola, Anthrax
Following passage of the Patriot Act in 2001 and the Bioterrorism Preparedness Act the next year, the efficiency of research on Ebola virus and Bacillus anthracis, both considered "weaponizeable" microorganisms, dropped, according to Elizabeth Casman of Carnegie Mellon University in Pittsburgh, Pa., and her collaborators. Although the numbers of papers being published on these microorganisms and related topics increased after 2002, there was a two- to fivefold increase in the cost of doing research on these and other select agents as measured by the number of research papers published per millions of U.S. research dollars awarded, they report, noting: "The decreased efficiency is likely due to the increased costs of and bureaucratic hurdles to conducting such research." Details appear in the May 25, 2010 Proceedings of the National Academy of Sciences (107:9556-9561).