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Cambridge, MA, United States

Helicos BioSciences Corporation, NASDAQ: HLCS was a publicly traded life science company headquartered in Cambridge, Massachusetts focused on genetic analysis technologies for the research, drug discovery and diagnostic markets. The firm's Helicos Genetic Analysis Platform was the first DNA-sequencing instrument to operate by imaging individual DNA molecules. In May 2010, the company announced a 50% layoff and a re-focusing on molecular diagnostics. After long financial troubles, in April 2010, Helicos was delisted from NASDAQ.Helicos was co-founded in 2003 by life science entrepreneur Stanley Lapidus, Stephen Quake, and Noubar Afeyan with investments from Atlas Venture, Flagship Ventures, Highland Capital Partners, MPM Capital, and Versant Ventures. Helicos's technology images the extension of individual DNA molecules using a defined primer and individual fluorescently labeled nucleotides, which contain a "Virtual Terminator" preventing incorporation of multiple nucleotides per cycle. The "Virtual Terminator" technology was developed by Dr. Suhaib Siddiqi, while at Helicos Biosciences.In the August 2009 issue of Nature Biotechnology, Dr. Stephen Quake, a professor of bioengineering at Stanford University and a co-founder of Helicos BioSciences, sequenced his own genome, using Single Molecule Sequencing for under $50,000 in reagents.On November 15, 2012, Helicos BioSciences filed for Chapter 11 bankruptcy. Wikipedia.

Ozsolak F.,Helicos BioSciences
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Methods for in-depth characterization of transcriptomes and quantification of transcript levels have emerged as valuable tools for understanding cellular physiology and human disease biology, and have begun to be utilized in various clinical diagnostic applications. Today, current methods utilized by the scientific community typically require RNA to be converted to cDNA prior to comprehensive measurements. However, this cDNA conversion process has been shown to introduce many biases and artifacts that interfere with the proper characterization and quantitation of transcripts. We have developed a direct RNA sequencing (DRS) approach, in which, unlike other technologies, RNA is sequenced directly without prior conversion to cDNA. The benefits of DRS include the ability to use minute quantities (e.g. on the order of several femtomoles) of RNA with minimal sample preparation, the ability to analyze short RNAs which pose unique challenges for analysis using cDNA-based approaches, and the ability to perform these analyses in a low-cost and high-throughput manner. Here, we describe the strategies and procedures we employ to prepare various RNA species for analysis with DRS.

Ozsolak F.,Helicos BioSciences
Current Issues in Molecular Biology | Year: 2016

With the introduction of next-generation sequencing (NGS) technologies in 2005, the domination of microarrays in genomics quickly came to an end due to NGS’s superior technical performance and cost advantages. By enabling genetic analysis capabilities that were not possible previously, NGS technologies have started to play an integral role in all areas of biomedical research. This chapter outlines the low-quantity DNA/ cDNA sequencing capabilities and applications developed with the Helicos single molecule DNA sequencing technology. © 2015, Caister Academic Press. All rights reserved.

Geisberg J.V.,Harvard University | Moqtaderi Z.,Harvard University | Fan X.,Harvard University | Fan X.,E.I. Du Pont de Nemours and Company | And 3 more authors.
Cell | Year: 2014

We measured half-lives of 21,248 mRNA 3′ isoforms in yeast by rapidly depleting RNA polymerase II from the nucleus and performing direct RNA sequencing throughout the decay process. Interestingly, half-lives of mRNA isoforms from the same gene, including nearly identical isoforms, often vary widely. Based on clusters of isoforms with different half-lives, we identify hundreds of sequences conferring stabilization or destabilization upon mRNAs terminating downstream. One class of stabilizing element is a polyU sequence that can interact with poly(A) tails, inhibit the association of poly(A)-binding protein, and confer increased stability upon introduction into ectopic transcripts. More generally, destabilizing and stabilizing elements are linked to the propensity of the poly(A) tail to engage in double-stranded structures. Isoforms engineered to fold into 3′ stem-loop structures not involving the poly(A) tail exhibit even longer half-lives. We suggest that double-stranded structures at 3′ ends are a major determinant of mRNA stability. © 2014 Elsevier Inc.

Helicos BioSciences | Date: 2011-10-27

The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids.

Ozsolak F.,Helicos BioSciences | Milos P.M.,Helicos BioSciences
Wiley Interdisciplinary Reviews: RNA | Year: 2011

Methods for in-depth genome-wide characterization of transcriptomes and quantification of transcript levels using various microarray and next-generation sequencing technologies have emerged as valuable tools for understanding cellular physiology and human disease biology and have begun to be utilized in various clinical diagnostic applications. Current methods, however, typically require RNA to be converted to complementary DNA prior to measurements. This step has been shown to introduce many biases and artifacts. In order to best characterize the 'true' transcriptome, the single-molecule direct RNA sequencing (DRS) technology was developed. This review focuses on the underlying principles behind the DRS, sample preparation steps, and the current and novel avenues of research and applications DRS offers. © 2011 John Wiley & Sons, Ltd.

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