Roche Introduces New DNA Sequencing Technology

Roche has unveiled its proprietary Sequencing by Expansion (SBX) technology, marking its return to the next-generation sequencing (NGS) space. SBX introduces a new biochemical approach designed to address the limitations of current sequencing technologies, particularly in speed, scalability, and signal clarity. The technology was presented shortly before the Advances in Genome Biology and Technology (AGBT) conference, accompanied by a technical webinar led by Mark Kokoris, vice president and head of SBX technology at Roche.

SBX represents the integration of developments from two of Roche’s earlier acquisitions—Stratos Genomics and Genia Technologies—and its core innovation lies in converting DNA into an expanded surrogate molecule called an Xpandomer. Approximately 50 times longer than the original DNA strand, the Xpandomer overcomes the spatial resolution and signal-to-noise challenges inherent in conventional nanopore sequencing. This conversion employs expandable nucleotide triphosphates (X-NTPs) that integrate highly distinguishable reporter codes and translocation control elements to enable efficient and accurate sequencing.

Xpandomers are processed through a complementary metal-oxide semiconductor (CMOS)-based sensor array with approximately eight million microwells, facilitating parallel high-throughput, single-molecule sequencing.

Roche reports several key advantages of SBX technology:

• Flexible operation adaptable to various sample requirements.
• High accuracy, demonstrated with F1 scores of over 99.80% for single nucleotide variants (SNVs) and over 99.48% for insertions and deletions (InDels) in HG001 whole genome samples.
• Very high throughput, capable of sequencing seven human genomes in one hour at 30X coverage.
• Flexible read lengths, ranging from 50 base pairs (bp) to over 1,000 bp.
• Ultra-fast workflow options, allowing processing from blood sample to variant call format (VCF) file in under eight hours.
• Cost efficiency supported by a scalable, reusable sensor module.

The development of SBX traces back to Mark Kokoris, a biochemist who began his research journey in the late 1980s at the University of California, Davis. Initially focused on molecular evolution and manual Sanger sequencing, Kokoris later applied his expertise in protein engineering to develop novel enzymes for gene therapy applications. His early experimentation in the field laid the groundwork for SBX, particularly in addressing the signal-to-noise challenges inherent to nanopore sequencing.

In 2007, Kokoris co-founded Stratos Genomics, where he and his team worked with limited resources to develop the SBX concept. According to Genetic Engineering and Biotechnology News (GEN), early experimentation was conducted with makeshift laboratory setups; then, from 2014 to 2019, collaborative research projects with Roche Diagnostics further refined the SBX chemistry, leading to Roche’s acquisition of Stratos Genomics in 2020. The breakthrough came after nearly a decade of experimentation when Kokoris and his team identified a stabilizing molecular additive that allowed the expanded DNA structures to form successfully.

Initially, SBX will be available for research use only, with early access expected later this year and commercialization planned for 2026. While details on pricing and sample preparation have not been disclosed, Roche intends to extend the technology's applications into clinical settings over time.

Roche’s introduction of SBX marks a renewed focus on sequencing after previous ventures, including the acquisition of 454 Life Sciences in 2007 and Genia Technologies in 2014. The company ended its 454 platform in 2013 due to competitive pressures from Illumina and other providers.

Topics: Tools & Methods