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Roche Rolls Out New DNA ‘Sequencing-by-Expansion’ Approach

Roche has put forward a new approach to genetic analysis, which it describes as sequencing-by-expansion—a proprietary method that pulls apart the DNA molecule and amplifies the signal of each individual base.

The company said its technique—which combines aspects of DNA synthesis and nanopore-based molecule reading—can avoid the time requirements of cycle-based sequencing as well as the comparable difficulties in distinguishing true signals among the noise.

Dubbed SBX, it’s the long-awaited fruit of two of Roche’s previous acquisitions: Stratos Genomics, the inventor of sequencing-by-expansion technology, purchased in 2020; and Genia Technologies, bought in 2014 for its massively parallel, single-molecule nanopore platform.

The process starts by copying over a single strand of DNA into its counterpart assembled of As, Gs, Cs and Ts, but ones that each come attached to a much larger, loop-shaped molecule coded to match its base.

Once the new molecule is complete, the inner backbone of the DNA is broken. The loops then expand to their full length, as the helix unwinds to as much as 50 times longer than before. This allows each gene to be read with greater clarity, as the bases were previously separated by the width of only a few atoms.

The unfurled, amplified strand of DNA code, called an Xpandomer, is then fed through the nanopores, where changes in electrical voltage correspond to each letter of the genetic sequence.

“The science behind SBX technology represents a significant breakthrough that addresses the limitations of existing sequencing solutions,” Roche Diagnostics CEO Matt Sause said in a statement ahead of the annual Advances in Genome Biology and Technology conference in Florida.

“By integrating and enhancing the two technologies, Roche’s SBX has created a differentiated approach, offering unparalleled speed, efficiency and flexibility,” Sause added. “The speed and accuracy of SBX has the potential to revolutionise the use of sequencing in research and healthcare.”

Though the technology is still in development and not yet commercially available, Roche said the approach could one day be suitable for whole genome and exome sequencing as well as parsing RNA, offering applications in research labs and potentially clinical testing.

The company also described it as scalable, and capable of tackling large and small projects—and slated it for a launch in 2026.

“Solving the signal-to-noise challenge is a key efficiency driver for the technology,” said Mark Kokoris, head of SBX technology at Roche Diagnostics, and former co-founder and CEO of Stratos. “With this capability we can flexibly operate across a range of throughput scales using the same sequencing system, which provides a significant advantage to users.”

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