Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Biotech Lock-Up Expiration Hell Portfolio -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (296)	8/7/2001 6:57:40 AM
From: nigel bates	Read Replies (1) \| Respond to of 1005

MADISON, Wis., Aug. 7 /PRNewswire/ -- Scientists at Third Wave Technologies Inc. (Nasdaq: TWTI - news) have demonstrated the ability to analyze genetic sequences based on their structure, a dramatic departure from conventional methods that require the linear analysis of a sequence under tightly controlled conditions. The scientists' findings, published in the current issue of ``Nucleic Acids Research,'' are a technological breakthrough with the potential to revolutionize nucleic acid (DNA and RNA) sequence analysis and dramatically simplify research and clinical applications by requiring fewer probes and far less sophisticated instrumentation, which could enable easy, inexpensive analysis directly at the point of patient care. ``Third Wave's structure-specific sequence analysis technology has the potential to radically reshape the landscape of nucleic acid analysis by allowing the detection of genetic variations more easily, efficiently and inexpensively than current, linear analysis methods,'' said Lance Fors, Ph.D., chairman and chief executive officer of Third Wave. Because nucleic acids have a natural tendency to fold on themselves, traditional hybridization assays and arrays must use a variety of methods to overcome the interference created when they do, adding multiple steps and additional cost to the analysis. Third Wave's structure-specific hybridization approach, however, eliminates those steps -- and their expense -- by using the structure of the nucleic acid to detect variations anywhere in the molecule of interest. The number of probes needed for structure-specific analysis is reduced because the probes bridge the unique, three-dimensional structure of a single, folded strand of DNA or RNA rather than targeting its linear sequence. In addition, structure-specific analysis can be performed on the benchtop at room temperature on simple instruments that are now widely used in hospitals, clinics and physicians' offices because the method targets the nucleic acid's natural structural fingerprint. The ability to genotype variations by structure is important in the diagnosis of disease, particularly viral disease. In the case of the hepatitis C virus (HCV), for example, there are numerous changes in the RNA sequence of the virus that do not determine genotype. Some of these changes either do not affect the structure or are offset by other changes that permit functionally important structural features in the genome to be conserved. However, sequence changes associated with specific viral genotypes (HCV 1a, 1b, 2a/c, 3a, etc.) are associated with changes in the genome structure that allow different genotypes to be easily distinguished by structure-specific probing. The same relationship between structure and function exists in many other genetic sequences, as well. Structure-specific sequence analysis can, therefore, quickly determine functionally significant sequence changes without the need for base-by-base sequence determination. Key Findings Reported in Nucleic Acids Research: Structure-Specific Analysis * Simplified probe sets for complex analysis. The need for fewer probes makes test development, manufacturing and use simpler and less expensive. Genotyping HCV isolates using structure-specific sequence analysis, for example, used half as many probes as would be needed for conventional, linear analysis methods. * Easier genotyping -- potentially enabling analysis at point of care. Structure-specific sequence analysis detects changes under a broad range of conditions, including room temperature, which could lead to simple, accurate analysis at the point of care. Mismatch-based hybridization tests rely on small changes in the stability of a probe bound to a target nucleic acid at high temperatures, where temperature conditions must be precisely controlled. * Better discrimination. Genotyping using structure-specific probes showed discrimination between genotypes of up to 25:1, compared to ratios of between 5:1 and 10:1 obtained with conventional, linear analysis methods. * Structure Modeling. Combining structure-specific enzymatic probing with computational analysis of genome structure allows identification of the correct secondary and tertiary structures of individual sequences. A comparison of multiple genetic sequences from many related species was previously required. * Detection of long-range DNA interactions. Structure-specific probes were able to detect sequence changes hundreds of bases from the probe-binding site. Mismatch-based approaches require the probe to bind at the site of the suspected mismatch. ``The power of structure-specific sequence analysis is in its combination of flexible test conditions with powerful discrimination capability,'' Fors said. ``This technology is ideal for the high-volume analysis needed for pathogen genotyping and mutation discovery research.'' The authors of the Nucleic Acids Research paper are Third Wave scientists Fang Dong, Hatim Allawi, Todd Anderson, Bruce Neri and Victor Lyamichev.