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Stratos Genomics Develops Disruptive Gene Sequencing Technology

Seattle–based, Stratos Genomics Inc, an innovator in molecular engineering and gene sequencing techniques, announced today the successful demonstration of nanopore sequencing with their proprietary expandable nucleotides (X-NTP™) utilizing a novel single molecule detection method.

This advance–single molecule detection of long DNA sequences–builds upon previous success in which longer 210 and 36 base template sequences were the foundation of earlier work by the company.

Stratos’ Sequencing by Expansion technology (SBX™) represents a new platform for a low cost and more rapid method for whole genome sequencing. In a nutshell, SBXTM “is an efficient, low-cost DNA preparation method that rescales a DNA target into a longer surrogate polymer,’’ according to the company’s recent press release.

This surrogate–referred to as an Xpandomer™–is a reproduction of sequence data using what is known as “high signal-to-noise reporters,” thus allowing rapid identification of specific base sequences. This approach allows for single molecule detection of long sequences using small, low cost, nanopore instruments, also allowing for alternative measurement approaches. Representing a major advance, Stratos’ X-NTP sequencing was developed using a proprietary DNA polymerase to incorporate the expandable nucleotides.

“One year ago, we set a challenging goal to sequence X-NTP based Xpandomers in a nanopore prior to June and we accomplished it,” said Mark Kokorois, Stratos Genomics President and Chief Scientific Officer. “With the fundamental processes in place, our focus is now on optimizing for commercial level performance,” added Kokoris.

Roche , in June 2014, made a key investment in Stratos Genomics embarking on a research collaboration to pursue additional development of the specific technology enabling a transition to single molecule sequencing of DNA fragments with the aid of protein nanopores.

Over the past year, Roche has been partnering with Stratos to develop low-cost and rapid preparation techniques for DNA Xpandomers™. Roche’s expertise in polymerase mutagenesis, design of protein nanopores, modified nucleotide chemistries and rare reagent manufacturing was invaluable to the joint effort.

“The milestone sequencing results are promising,” explained Vinod Makhijani, Vice President and Project Leader, Roche Sequencing Business Development. “While several technical challenges remain on the path towards commercial readiness, we’re optimistic about our ability to tackle them with the joint expertise and resources of the Roche-Stratos team.”

“Roche Ventures and Fisk Ventures both have exercised their right under last year’s Series B financing to purchase additional shares based on our milestone success. Roche will invest an additional $10 million and Fisk Ventures $5 million. This will complete our $30 million Series B funding,” said Allan Stephan, CEO, Stratos Genomics.

The aim of Stratos Genomics, according to Stephan, is to make SBX the preferred method of DNA sequencing by ultimately making the ‘Sequencing by Expansion’ (SBX™) method low cost, rapid and widely available. SBX represents ground-breaking technology, utilizing a single-molecule detection method that removes the limitations of current, potentially error-prone sequencing technologies, essentially by promoting allowing a low-cost, rapid alternative to whole genome sequencing.

There are some companies that have attempted single molecule sequencing in different variations, including Pacific Bio and Oxford Nanopore, explains Stephan. However, Stratos’ patented single molecule detection technology, remains unique in their field of competitors at this stage.

One of the most widespread techniques currently available for genome sequencing–known as sequencing by synthesis (SBS)- was developed by Ilumina, based in Menlo Park, California.

SBS relies on creation of a large “forest” of uniform DNA segments, “almost like a field of the exact same pieces of DNA you are going to be measuring”, explains Stephan. The process involves floating in individual nucleotides with fluorescent capability. When a specific nucleotide is incorporated, your get a burst of light that optics can detect. “It’s a serial process of flooding in these nucleotides and reading the optical signatures that comes out of it”–which can be cumbersome “and involve big machines” described Stephan.

In comparison– in single molecule detection—as Stephan explains, “you don’t have to rely on an enormous ‘forest’ to give you a signal, but instead are getting a signal from the individual expandable base–using an Xpandomer.”

The single molecule detection approach to sequencing clearly represents a potentially disruptive technology in gene sequencing, as Stephan outlines.

“It can enable low cost, rapid, more accurate and targeted and whole genome sequencing, dropping the price into a range that is accessible by essentially everyone,” he concludes.

Source: Forbes

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