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GenDx Receives CE-IVD Marking for HLA Product; Inks Deal with PacBio

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NEW YORK (GenomeWeb) – HLA typing firm GenDx said this week that it has received CE-IVD marking for its next-generation sequencing amplification kit for HLA typing. In addition, last week the Dutch firm and Pacific Biosciences said they have entered into a co-marketing agreement for HLA sequencing.

The CE-marked amplification kit, NGSgo-AmpX, can be used with Illumina's MiSeq system, Life Technologies' Ion Torrent PGM, or the PacBio RS, and will also work with Sanger sequencing.

GenDx spun out from the University Medical Center in Utrecht, the Netherlands in 2005. It originally offered products in the area of sequence-based typing for transplantation, but has expanded into next-generation sequencing and now provides products, services, and software using both conventional Sanger-based methods and next-gen sequencing.

According to Wietse Mulder, co-founder and managing director, the company is platform agnostic, and it is designing NGS products that can be adapted to the MiSeq, PGM, or RS systems.

The CE-IVD-marked NGSgo-AmpX product uses Qiagen's LongRange polymerase to amplify all Class I HLA genes (HLA-A, HLA-B, and HLA-C) and Class II HLA genes (DRB1, DRB3/4/5, DQB1, DQA1, DPB1, and DPA1.

According to Mulder, the amplification strategy uses multiple primers for each gene to ensure complete coverage. Sequencing the HLA genes can be tricky, he said, because they contain around 11,000 different variants. For clinical purposes, it is important to make sure the various alleles are phased. When next-gen sequencing was first looked at as a possible tool for HLA typing, he said that researchers would often not sequence the entire gene and would just target specific exons, because it was easier to do. However, "you have to be sure that a SNP in exon 2 is linked to exon 3, exon 4, and so on," Mulder said. "If you only sequence exon by exon, you can't solve this problem."

Besides its CE-IVD-marked amplification kit, GenDx also offers research-use only products for fragmentation, library prep, adding the appropriate adaptors and indices for sequencing and sample identification, and analysis. He said that its NGSengine for analysis would help to set the company apart from competition.

One facet of the firm's software that Mulder said is unique is that it does not use a fixed reference genome when aligning reads. Because the HLA genes have so many variants, there is no one single reference that can be used, he said, so GenDx uses a "dynamic reference," which enables more accurate typing.

Mulder said that in the future, the company plans to develop a full CE-IVD-marked kit for HLA typing on the MiSeq. The product will initially be sold for diagnostic purposes in Europe, but Mulder said that the company is also evaluating the regulatory space in the US. GenDx is also developing a full HLA kit for the PGM.

As part of its collaboration with PacBio, the company is focusing on developing an amplification strategy and will make barcoding primers. However, because of PacBio's agreement with Roche covering diagnostic products, GenDx will not develop and market an entire HLA typing kit, Mulder said, adding that "the collaboration is mostly focused on the first step in the workflow."

PacBio struck a $75 million agreement with Roche Diagnostics last year to develop and supply diagnostic products, including sequencing systems and consumables based on PacBio's SMRT technology. Under the terms of the agreement, Roche has exclusive rights to market the sequencing system and assays for clinical use. The companies have not disclosed what types of assays they will develop, but PacBio CEO Mike Hunkapiller has previously highlighted the HLA typing market as important for the company and an area where the RS system's long reads would be particularly helpful.

The NGS HLA typing market has heated up recently, and Mulder said that he anticipates that most labs will use NGS for HLA typing within the next three to four years. NGS has been a "disruptive technology in the HLA field," he said.

Mulder said that the HLA typing field has two main markets. On one hand, he said, donor registries want to be able to type many samples as cost efficiently as possible. That need for high throughput and low cost must be balanced with the need for also obtaining as much information about a donor's HLA type as possible, which leads to more accurate matching and better outcomes.

Smaller clinical labs don't need as much throughput as the large registries, he said, but do need fast turnaround and low cost. These labs also will have different requirements for the level of resolution needed depending on the specific clinical application. For instance, organ transplantation does not require as high a resolution as bone marrow transplantation, he said.

Aside from GenDx, a number of firms are looking to enter the HLA typing space with NGS-based products and services.

NGS interpretation firm Omixon recently said it plans to develop an HLA kit based on the clinical service offering at the Children's Hospital of Philadelphia.

HLA typing firm HistoGenetics has incorporated into its workflow a targeted sequencing HLA typing panel that it runs on its 30 MiSeqs. It processes between 80,000 and 100,000 samples per month, primarily from donor registries. The company has also purchased two PacBio RS systems that it is validating for clinical HLA typing.

In addition, Illumina has said it will market an HLA typing assay on either the MiSeqDx or MiSeq system by the middle of the year to tap into the nearly $300 million HLA typing market. It has said that its assay will be based on its TruSight chemistry and will consist of eight HLA genes that will be sequenced completely and fully phased.

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