Twist Introduces Double-Stranded DNA Probes in a First for Exome Sequencing

We recently caught up with Dr. Emily Leproust, CEO of Twist Bioscience, to discuss her company's innovative offerings at the recent Advances in Genome Biology and Technology Conference (AGBT) in Orlando.

Twist have unveiled a suite of products aimed at enhancing Next Generation Sequencing. These include a Human Core Exome Kit, a library preparation and target enrichment kit, and Custom Panels that can be made to individual request.  

Ruairi Mackenzie (RM): Your exome and targeting enrichment kits’ probes use double-stranded DNA, which is unique within the industry. What are the advantages of this approach?

Dr. Emily Leproust (EL): Traditionally, probes in double-stranded form have been thought to bind with each other and compete against the formation of target-probe hybrids and in fact, all of the other exome and custom kits in the market today use either single-stranded DNA or RNA. We’ve developed a proprietary method to enable double-stranded probes without compromising target capture. This innovation significantly differentiates our offering by enabling specific capture of both strands of the target, resulting in an increase in the number of unique molecules sequenced and allowing for detection of strand-specific mutations such as deamination events in ancient samples or FFPE. Being able to tease out real and rare mutations from nucleotide changes due to processing or degradation is critical especially in cancer sequencing.

RM: What are the other innovations of your exome and target enrichment solutions announced at AGBT?

EL: In addition to the double-stranded probes, we've added optimized amplification and NGS QC of the probes, resulting in extreme uniformity of the enriched targets with unparalleled specificity. Importantly, we believe the uniformity of our capture means you no longer over sequence your samples - providing future cost savings in terms of increasing the number of samples you can run, increasing the depth of coverage or reducing overall costs.

With this enrichment platform, we offer exceptional quality and performance by maximizing capture efficiency with the added value of being able to customize the enrichment solution from panel design to kit configuration. This flexibility allows the end user the ability to really tailor their enrichment solution to their application without compromise. In addition, with our rapid custom design pipeline, targeted panels can be optimized quickly, allowing the user to scale with minimal time.

RM: Can you talk us through some of the applications of your Custom DNA Capture Panels?

EL: Several of our customers will be presenting at Advances in Genome Biology and Technology who have used our custom panels: Foundation Medicine, which is a cancer research company; USAMRIID, who use our probes for viral outbreak research and with whom we worked in partnership with Illumina to develop a custom panviral panel.

In general terms, we would sell to customers interested in conducting genetic and genomic research.  For the custom panels in particular, we anticipate it will largely be used by cancer researchers interested in a specific segment(s) of the genetic sequence; however, as genetic research escalates exponentially, we expect that it could be used in a much wider array of research - from antibiotics to antibodies to viruses and bacteria.

For instance, a pharmaceutical company doing drug development may only be interested in the kinases, or a physician looking at mutations driving cancer in a patient may only be interested in the 100 or 1,000 genes associated with a particular cancer, or researchers may only be interested in chromosome 18. So, for those people only interested in just a fraction of the genome, we are providing a solution that meets their exact needs.

RM: Do your latest announcements represent Twist’s first foray into NGS solutions? If so, I’d like to ask what prompted you to move into this field, and where you think NGS is going next?

EL: This is indeed our first foray into NGS solutions. Our R&D team identified a proprietary way to approach the exome and custom target enrichment market leveraging the power of our synthetic DNA platform. We believe this is an excellent way to enter an adjacent market in a way that builds on our core competencies in making synthetic DNA. 

NGS is a very exciting market - initially, exome sequencing was very exciting given the fact that it reduced the cost of sequencing significantly. As the cost of whole genome sequencing has come down substantially, more organizations are moving to a WGS model. With the introduction of the Twist solutions, we believe we will be able to bring back the popularity of exome and custom sequencing, given the uniformity of our probes and the cost savings for future sequencing because of that uniformity. We are very excited about the future, and believe that through NGS, we as a society are moving toward personalized and precision medicine. We look forward to participating in that revolution through our exome and custom solutions.

Dr Emily Leproust was speaking to Ruairi Mackenzie, Science Writer for Technology Networks.