NEW YORK (GenomeWeb) – Swedish startup Vanadis Diagnostics, recently acquired by PerkinElmer, has been quietly working on a fully automated noninvasive prenatal aneuploidy test that promises lower cost and greater ease of use than existing NIPTs and requires neither next-gen sequencing nor microarray technology.
PerkinElmer, a leader in prenatal serum screening and newborn screening, said last week that it had acquired Vanadis for an undisclosed amount. The deal marks the company's first direct move into the cell-free DNA-based NIPT market — three years ago, PerkinElmer announced a marketing agreement with Verinata, now owned by Illumina. "The Vanadis platform will enable PerkinElmer to offer a simplified, cost-effective, high-throughput approach to NIPT to help facilitate wider access for pregnant women," PerkinElmer said in a statement.
The company is entering the NIPT market at a relatively late stage, moving into an already crowded field. After initially offering their tests as a service, companies like Illumina, Roche's Ariosa Diagnostics, Sequenom, and Natera are increasingly transferring or licensing their NIPT technology to other laboratories. In addition, newcomers like Premaitha Health, NIPD Genetics, and Singlera Genomics have burst onto the scene, with Premaitha and Multiplicom offering the only CE-marked in vitro diagnostic NIPTs so far.
However, PerkinElmer maintains that many traditional biochemistry prenatal testing labs have found it challenging to implement NIPT technology, due to the complexity of the tests and the large capital investment in instrumentation required. "Vanadis' simplified NIPT platform, once available, should help overcome these obstacles, giving labs a wider range of prenatal testing capabilities and providing important information to physicians and patients," Prahlad Singh, PerkinElmer's president of diagnostics, said in a statement.
PerkinElmer declined to provide further information about the acquisition or its plans for commercializing Vanadis' platform. However, Vanadis presented an outline of its technology and talked about its development at a meeting of the Fetal Medicine Foundation in London in early December.
Olle Ericsson and Fredrik Dahl co-founded Vanadis, based in Sollentuna, north of Stockholm, in late 2013. The two had previously founded Halo Genomics, first called Olink Genomics, which commercialized a probe-based single-tube multiplex amplification methodology, known as Selector technology, that was originally developed at Uppsala University. Agilent Technologies acquired Halo Genomics in 2011.
Prior to the acquisition, Vanadis was funded by Swedish angel investors, primarily a group called 20 North Street that is part of Swedish corporate finance advisory firm HDR Partners. According to HDR's website, PerkinElmer acquired Vanadis in December 2015 and both founders will stay on as employees of PerkinElmer in Sweden.
Interestingly, Ann-Christine Sundell, until 2010 president of PerkinElmer's genetic screening business, had been a member of Vanadis' board since the firm was founded.
Ericsson, Vanadis' CEO, said the company's goal is to develop a cell-free DNA-based prenatal aneuploidy test for all women that offers laboratories both low cost and user-friendliness and could eventually replace the first trimester combined test. "When we talked to people in the [prenatal testing] space, it was clear that everyone wanted to do [NIPT] … but it was much too expensive to do and it was complicated," he recently told GenomeWeb, "so we wanted to solve those two problems."
Vanadis' so-called Smart NIPT technology shares the fundamental principle of manipulating DNA with oligonucleotide probes with Halo Genomics' Selector technology, but "it is designed in a very different way that is dedicated to aneuploidy measurements," Ericsson said.
After extracting cell-free DNA from maternal plasma, chromosome-specific probes are added that capture several thousand DNA fragments from each target chromosome, initially chromosomes 21, 13, and 18. "The trick is to do that very specifically, so you only get fragments you're interested in, from the right chromosomes," Ericsson explained, noting that the company spent a lot of time optimizing the probes.
Using DNA ligase and polymerase, the DNA fragments are then converted into DNA circles. Rolling circle amplification copies the circles into long DNA chains, which collapse into ball-shaped "DNA objects." These can be labeled with fluorescent probes, which are designed in a way that all DNA objects originating from the same chromosome are labeled with the same color. Each DNA ball receives about 1,000 fluorophores.
The DNA objects are then loaded onto a company-developed 96-well plate with a nanofilter at the bottom that retains the DNA balls but washes away free fluorophores and other reagents. Subsequently, the DNA objects are imagined from below through the filter, and counted automatically, using standard fluorescent imaging technology. An overabundance of DNA objects from one chromosome indicates a trisomy, with the DNA from the two other chromosomes serving as controls.
The nanofilter plate "was a key component we developed because it enables us to use a 96-well format and capture all the DNA objects on the bottom and image from below," Ericsson said. "That was actually pretty tricky to get to work because it needs to be a very flat surface, and it has to be transparent, and it has to be a filter."
The entire workflow, from receiving a blood sample to obtaining results, takes about two to three days. Several aspects of the technology are patent-protected, he said, including the conversion of DNA targets into DNA objects and the read-out method. At the December meeting, Vanadis presented results from a clinical proof-of-principle study that involved 183 blood samples from pregnant women, collected between weeks 10 and 18 of gestation, which the company analyzed blindly. Using one well per patient on a 96-well plate, and counting more than 200,000 DNA objects per chromosome, company scientists were able to classify all 15 trisomy 21-positive samples correctly.
Additional clinical studies are ongoing, Ericsson said, and the company is looking for more collaborators.
Vanadis has been developing the test to detect trisomies 21, 13, and 18, he said, but it could be expanded in the future to include other chromosomal abnormalities. The goal is to price the test in a way that the all-in cost for a laboratory would be no more than the cost of the current first trimester combined screen, on the order of $100 to $200, he said.
Prior to PerkinElmer's acquisition, the company had planned to commercialize the test for research use only in 2016 and as a CE-marked IVD product in 2017.