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Helicos BioSciences Corporation ({{NASDAQ}}|HLCS) is a life sciences company focused on genetic analysis technologies for the research, drug discovery and clinical diagnostics markets. Their first product, the HeliScope system, is based on true Single Molecule Sequencing (tSMS), a technology based on research by Dr. Stephen Quake which enables rapid analysis of large quantities of genetic material by directly sequencing single molecules of DNA or single DNA copies of RNA. This differs from traditional DNA Sequencing, in which experimentation is done on copies of DNA, rather than the original DNA itself. The importance of this distinction is that tSMS eliminates much of the costly, time-consuming sample preparation techniques currently in use, such as PCR amplification or cloning. It is hoped that this reduction of overhead, combined with the increased throughput of the HeliScope, will better enable researchers and scientists to run genetic testing on large populations, leading to highly efficient drug discovery and personalized medicine.

tSMS Technology

After genomic DNA is sheared, poly-A tails with a terminal Cy3-labeled nucleotide are added to both ends of the DNA fragments. The Cy3 label is used to localize the templates once they are bound to immobilized oligo-dT primers on the surface of the flow cell. Next, the polymerase and Cy5-labeled nucleotides are added, and incorporated bases are detected. The label is cleaved, and the process is repeated for multiple cycles to generate strand lengths required for specific applications. The technology is also capable of de novo sequencing - an antisense copy of the single-molecule template is produced enzymatically using the immobilized oligo-dT base as a primer. The antisense strand is sequenced from the 5´ end, after which a predetermined number of cold or unlabeled nucleotides are added to form a continuous, complementary strand. Next, another round of sequencing is initiated using the single molecule process. This combination can be reiterated with various amounts of cold nucleotides on long templates, generating sequence information from the same template for contig assembly.^[1]

References

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