분자유전학실험실 (단국대학교 분자생물학과)



 송민선 ( 2006-02-08 22:04:49 , Hit : 4438
 nbt0602supp_BE18_I1.gif (8.5 KB), Download : 80
 http://www.nature.com/nbt/journal/v20/n6s/full/nbt0602supp-BE18.html
 Nature에 실린 Private company profiles for Archemix


이번에 교수님께서 다녀오신 Archemix회사에 대하여, nature에 실린 글을 upload  합니다.^^

Nature Biotechnology  20, BE18 - BE19 (2002)
doi:10.1038/nbt0602supp-BE18
Archemix
Liz Fletcher


An RNA evolution in drug discovery?
  
RiboReporters can specifically recognize any desired target and generate easily detectable signals.

  
The drug industry is hungry for more versatile and cost-effective platforms for drug discovery and development. To meet this need, Cambridge, MA−based startup Archemix has chosen a novel starting material—oligonucleotides—for a range of biosensors and therapeutics. (Click here for company profile.)

In addition to their well-known function as information-storage molecules, RNA and DNA have other useful properties. For example, aptamers—short oligonucleotides (of either RNA or DNA)—can bind tightly to proteins, blocking their function. Alternatively, specialized RNA structures called ribozymes may act as enzymes, in one case snipping themselves out of longer oligonucleotide strands and deactivating genes.

According to David Epstein, senior director of research and development at Archemix, the aptamer and ribozyme technologies create a "forward-integrated company"—with ribozymes and aptamers providing the new drug discovery tools, and aptamers providing the novel therapeutics. For such a young company, Archemix has an exceptionally rich intellectual property estate, owning or controlling 200 issued and pending patents on applications of aptamers and ribozymes. The mixed heritage of Archemix's patent estate is due to its founders' early shopping spree, which has left it possessing key intellectual property. The company was founded in May 2001 after acquiring ribozyme intellectual property from Ribozyme Pharmaceuticals (Boulder, CO) in exchange for equity. This was followed in October 2001 by the acquisition of aptamer intellectual property—the SELEX (for systemic evolution of ligands through exponential enrichment) system—from Gilead Sciences (Foster City, CA) for $17.5 million.

Ribozymes have predictable two-dimensional structures, and can be synthesized with ease in a combinatorial fashion to create thousands of variants with differing properties. Ron Breaker, now a scientific advisor for Archemix, evolved the means to create an "allosteric ribozyme" whose activity was contingent on the binding of any of a variety of analytes—metal ions, nucleotides, cofactors, or drugs—to a remote sensor region, an aptamer (see Nat. Biotechnol.  19, 336−341, 2001). After the analyte binds to the sensor region, the ribozyme is activated, in this case cleaving off a radiolabel, although other detector systems could be used (e.g., changes in fluorescence). This forms the basis of Archemix's RiboReporter platform, which it hopes to partner out with other drug developers.

The advantage of RiboReporters as a drug discovery tool is their versatility: "With one tool you can run an assay in solution, in tissues and cells, and on chips...we can now do in real time the gene profiling only dreamed of five years ago," says Epstein. Ribozymes were known to work in solution in vivo; now Archemix has shown them to be stable enough to place on microchips, which has proved difficult to do with proteins and antibodies. Archemix scientists have now developed RiboReporters able to detect very low concentrations of proteins, suitable for "protein PCR," says Epstein.

However, Archemix's future revenue may come from aptamer-based therapeutics. Short strands of nucleotides may seem unlikely drug candidates, but proof of principle has already been gathered by Eyetech Pharmaceuticals (New York). Eyetech in-licensed the aptamer EYE100, targeted against the extracellular protein vascular endothelial growth factor (VEGF), from NeXstar (subsequently acquired by Gilead), and has the product in phase 2/3 trials for the treatment of age-related macular degeneration.

Archemix has great hopes for other therapeutic aptamers, which, according to Epstein, are superior in several ways to monoclonal antibodies. Aptamers have low molecular weights and are therefore easier and cheaper to manufacture than larger biologicals. Moreover, once an aptamer has been selected in vitro, it requires little chemical manipulation to make it suitable for use as a drug in vivo. Archemix, it seems, is well positioned to offer monoclonal antibody developers some serious competition. LF








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