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NewGene Plans to Offer 454-Based Genetic Testing for UK's NHS, Other Clients by Early 2010

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NewGene, a UK-based molecular diagnostics startup, could soon be one of the first European laboratories to provide clinical genetic tests on 454's sequencing platform.

Toward the end of this year or in early 2010, the Newcastle upon Tyne-based company plans to offer the UK's National Health Service and other clients full-gene sequencing tests for several genetic conditions using Roche's 454 Genome Sequencer FLX. It expects to offer these tests at a lower cost and with a faster turnaround than existing providers using Sanger sequencing, NewGene said.

The company, which has eight full-time employees, is a partnership between the Newcastle Hospitals NHS Foundation Trust and Newcastle University, which provided it with an undisclosed amount of startup funding. It is housed in the same building as the university's Institute of Human Genetics, which is headed by a NewGene director.

NewGene, which acquired the 454 system in the spring of 2007, currently uses it for a variety of research service offerings for academic, government, and industrial clients. It also provides three molecular diagnostic tests at the moment: a quantitative PCR-based chronic myeloid leukemia monitoring assay, and two tests that run on the Sequenom platform: a chronic myeloid leukemia mutation assay and a BRCA1 and BRCA2 mutation analysis for Norwegian individuals.

NewGene is currently developing several full-gene sequencing tests that will run on the GS FLX for "clinically important genetic conditions," and the company expects them to become available "towards the end of this year," according to Ann Curtis, scientific director at NewGene. Among them are tests for the BRCA1 and BRCA2 breast cancer genes, three genes involved in hereditary colon cancer, several genes implicated in limb-girdle muscular dystrophy, and genes involved in atypic hemolytic uremic syndrome.

According to the UK Genetic Testing Network, a group of labs, clinicians, and providers of NHS genetic services, there are currently five UK labs that offer sequencing of the entire coding region of the BRCA1 and BRCA2 genes, four that offer sequencing for hereditary colon cancer, one that offers sequencing for limb-girdle muscular dystrophy, and one that offers sequencing for hemolytic uremic syndrome.

In addition, NewGene is working on a hereditary breast cancer screening test that will use the Sequenom platform to assay nonsense-mediated decay, measuring expression of the BRCA1 gene. That test should be available starting at the end of August, according to Curtis.

NewGene plans to offer the testing services primarily to the NHS but also to private and international healthcare services.

To develop and validate the amplicon-based sequencing tests, the company is working closely with the Northern Genetics Service, a clinical genetics service for the NHS that is based in Newcastle. The center currently provides the NHS services such as robotics and primers for PCR-amplification of the genes.

Through its partnership with the Newcastle Hospitals NHS Foundation Trust, NewGene also has access to clinical patient samples to help it validate its assays. "We have a large number of samples with known mutations, and we are now using them to validate [our tests] and show that we can get 100 percent pickup of known mutations," including "difficult mutations," such as small indels, Curtis said.

While diagnostic testing is "not quite as heavily regulated as the US," she said, "we will have to present our validation to ... lab accreditation bodies when that time comes."

NewGene plans to provide its tests at a lower cost and faster turnaround than existing providers that use Sanger sequencing, she added.

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"One of the challenges we face is continually maximizing the number of samples we can get on each sequencing run" in order to lower the cost per sample, said Jonathan Coxhead, NewGene's chief scientist. To that end, he and his colleagues are working on multiplexing strategies, using 454's multiplex identifiers for barcoding.

To capture and amplify the genes for sequencing, they have also "dabbled in NimbleGen technology," he said, but decided to focus on amplicon sequencing for now. "One of the aims is efficiency of sequencing on the machine. We can optimize that more specifically with amplicons, we think, at the moment," he said.

Roche has shown an active interest in the company's work, providing feedback and suggestions on assay design and being "receptive to the needs we might have" regarding data interpretation, according to Coxhead.

At the time NewGene chose its sequencing platform in 2007, it was attracted by 454's capacity and versatility. Also, the amount of data coming off the machine was "quite manageable" for a small team like his, Coxhead said, and the short overnight sequencing runs were attractive, although he acknowledged that in terms of sample preparation, the 454 is "one of the more time-consuming platforms out there." Back in 2007, Illumina's Genome Analyzer was still in its infancy, and Applied Biosystems' SOLiD was not yet available.

In terms of future improvements of the 454 platform, Coxhead said he looks forward to greater capacity and longer reads as well as more automation of the front-end preparation steps.

NewGene will likely be one of the first European laboratories to provide clinical testing on a second-generation sequencing platform, though others are working toward the same goal.

About a year ago, researchers at the Oxford Biomedical Research Center, a partnership between the Oxford Radcliffe Hospitals NHS Trust and the University of Oxford, said they plan to use both 454's and Illumina's sequencing platforms to develop multiple-gene tests for a number of cardiovascular and retinal diseases, to identify mental retardation, and to survey infections (see In Sequence 9/9/2008).

Also last year, researchers at the Blood Center Linz in Austria said they were using the 454 platform to develop a sequencing method for routine use in HLA typing (see In Sequence 9/2/2008).

However, not all providers of sequencing-based clinical tests are convinced second-generation sequencing is the way to go at the moment. Earlier this year, Nezih Cereb, president of HLA-typing firm HistoGenetics, told In Sequence that the sample prep for the 454 platform is currently not robust enough and the cost per run too high to make the technology interesting for his firm, which types up to 360,000 samples per year on 13 Applied Biosystems 3730xl capillary sequencers (see In Sequence 3/17/2009).

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