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Twist Bioscience Enters NGS Market With Launch of Target Enrichment Products

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NEW YORK (GenomeWeb) – Twist Bioscience entered the next-generation sequencing sample prep market this week with the launch of its first target enrichment products.

"We are very excited to enter the NGS space," said CEO and Cofounder Emily LeProust during a company-sponsored workshop at the Advances in Genome Biology and Technology conference in Orlando, Florida, this week. During the workshop, several early-access customers offered their first impressions of the new products, an exome capture product called Twist Human Core Exome Kit, a pan-viral panel, and custom panels.

The move underscores Twist's continued expansion into new areas that can benefit from its DNA synthesis platform. Its business is based on a proprietary and patent-protected DNA synthesis process that uses a silicon chip with 10,000 wells and allows it to make 1 million oligonucleotides in parallel. 

Since Twist's inception in 2013, it has raised $191 million from a variety of investors that include Illumina, WuXi Healthcare Ventures, and entrepreneur Yuri Milner. The company has locations in San Francisco, where it synthesizes DNA; South San Francisco, where its enzyme work takes place; Tel Aviv, where it does software development; and San Diego, and has grown to about 250 employees, said LeProust, who spoke with GenomeWeb at the sidelines of the conference.

Up until now, Twist has mainly focused on gene synthesis, oligonucleotide pools for CRISPR guide RNA libraries, antibody libraries for drug optimization, and on the nascent field of DNA data storage. Earlier this year at the JP Morgan Healthcare Conference, the firm said that it shipped more than 150,000 synthesized genes to almost 300 customers last year, and its goal for this year is to increase its gene synthesis capacity to 1 million genes.

NGS target enrichment, with an estimated market size of $500 million, represents another area for the company to compete in. The market has been served by several established players, including Agilent Technologies and its SureSelect and Haloplex products, Roche and its SeqCap and HEAT-Seq products, and Integrated DNA Technologies' xGen products. LeProust herself was involved with the launch of Agilent's SureSelect technology in 2009 and its development over several years.

Twist's enrichment kits can be ordered in different configurations that do or don't include library prep and enrichment reagents. The company's Human Core Exome Kit covers 33 megabases of protein-coding regions and uses 120-base-pair double-stranded DNA probes. Users can customize the kit by adding more content or enhancing the existing content.

Twist has also partnered with IntegraGen of France, offering customers the option to add IntegraGen's Mercury and Sirius platforms for germline or cancer sample analysis. In addition, IntegraGen plans to include Twist's enrichment products in its NGS service offerings.

Customers can also order panels for targets of their choice from Twist, which take two to three weeks to be delivered. The company allows customers to test the performance of their panel before they commit to a larger order in what it calls a "design-build-test-learn" cycle of optimization.

Like several of its competitors' products, Twist's DNA enrichment kits are based on hybridization capture of target DNA. However, according to LeProust, they offer a number of advantages.

For example, the company has found a way to synthesize and amplify pools of oligo probes more uniformly than other firms. As a result, customers can cover their targets with less sequencing, which saves costs. She declined to disclose how the company achieves greater uniformity because of a patent application that has not yet published but said that the method "leverages the power of our silicon chip."

Secondly, the company uses double-stranded rather than single-stranded DNA probes, so both strands of a DNA target are captured. This helps reduce the number of duplicates, she said, and is an advantage if one strand is difficult to capture but the other hybridizes well. It also enables researchers to distinguish between genuine mutations, which occur on both DNA strands, and DNA damage that only involves one strand, such as deamination in an FFPE sample.

Lastly, Twist checks the quality of all its probe libraries by next-gen sequencing prior to shipping, so customers can be sure that no probes are missing.

LeProust said that the target enrichment products are geared at several types of customers. Among them are researchers who currently use exome sequencing or targeted sequencing and are unhappy with costs and enrichment performance, which she said have not changed in years. Another group are users of CGH or genotyping arrays who are considering a switch to targeted sequencing. All those customers, she said, could benefit from the reduced cost of sequencing that the use of Twist's more uniform enrichment products affords.

During the company's AGBT workshop, several early-access customers presented on their experience with the new enrichment products. Shawn Levy, director of the Genomic Services Laboratory at the HudsonAlpha Institute, tested the Twist exome kit for FFPE sequencing last month, comparing it to the lab's existing workflow with Roche's SeqCap capture kit and using the Illumina NovaSeq for sequencing, and said that his "overall impression has been favorable." He commented on "index hopping," a problem with Illumina sequencers that use patterned flow cells, that led to some erroneous calls but could be fixed with the use of different index sets.    

Michael Wiley of the US Army Medical Research Institute of Infectious Diseases' Center for Genome Sciences has been using the Illumina TruSeq RNA Exome kit to characterize viral samples, and a probe set to study Zika virus strains, and he recently started supplementing these with a custom pan-viral probe set from Twist that includes 600,000 probes against about 1,000 RefSeq viral segments. He has been using these successfully to study Lassa virus samples from an outbreak in Liberia and other viral outbreaks.

In addition, Christine Malboeuf, director of clinical platforms at Foundation Medicine, recently included Twist in a comparison of capture methods for RNA sequencing from FFPE samples.  

Going forward, LeProust said, Twist plans to add more products and to expand its commercial reach by hiring more sales personnel and leveraging its e-commerce platform. It already has a sales team in the US and in Europe and plans to grow in Asia. Overall, the firm currently has 40 open positions.

In 2016, Twist also acquired Genome Compiler, an Israeli DNA software company, to help it build an e-commerce solution with gene design capabilities. Since last fall, that e-commerce platform has been available to existing customers, LeProust said, and the company is now opening it to more and more customers.     

Twist is also still embroiled in a lawsuit that LeProust's former employer, Agilent Technologies, brought in 2016 against Twist and several of its employees, claiming that LeProust and others stole genomics technology from Agilent, allegations Twist has denied. LeProust said the lawsuit has been "a distraction" and that she looks forward to being vindicated.

She said there is room for the company to grow in several areas it currently serves. For example, one goal is to replace cloning with gene synthesis, which is currently still more expensive.

DNA data storage is a "much bigger" market opportunity, estimated at $10 billion, she said, but will still take several years to develop. Twist has synthesized DNA for most of the recent publications on DNA storage, she said, and is collaborating with Microsoft and researchers at Columbia University in this area. "There is a lot of potential," LeProust said. "We have the ambition to continue to grow the company and be relevant in more and more markets."

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