The burgeoning market for noninvasive prenatal testing has to date been dominated by next-generation sequencing-based offerings, but that may change next year when CellScape launches its Clarity test.
And, according to its founder and executive chair, Karen Drexler, the firm believes its microarray-based offering will give it an advantage in the NIPT market, not only because it will at launch be able to test for the "top microdeletion syndromes" as well as other defects, but because of the market's familiarity with microarrays.
Drexler told BioArray News this week that one reason that CellScape decided to use arrays rather than other technologies is because the technology has already been adopted for invasive testing, meaning that potential clients who offer prenatal testing would already be familiar with the technology.
"We thought that invasive testing would start using arrays and thus the medical community would be trained to understand microarray analysis before we were ready to launch the Clarity test," she said.
In addition, she said that CellScape wants to "provide prenatally relevant information" and that "using a targeted microarray allows us to focus on what we believe — with lots of input from experts — to be the most important syndromes to assess prenatally."
Ultimately, the firm's decision was driven by its belief that "using microarrays would help the adoption of our test and would meet the market need."
CellScape's arrays are manufactured by Agilent Technologies.
Many of the other players in the NIPT market rely on next-generation sequencing platforms to conduct their tests. Some of these include Sequenom, new Illumina acquisition Verinata Health, Natera, and Ariosa Diagnostics. One company, Cellular Research, has received US National Institutes of Health funding to develop an array-based method for the prenatal detection of Down syndrome (BAN 1/8/2013). Elements of Cellular Research's technology were developed at Affymetrix, and Affy cofounder Stephen Fodor and former vice president of genotyping research Glenn Fu are involved with the firm.
Still, by focusing on certain conditions, such as Down syndrome, some view these other NIPT offerings as being narrower in scope compared to invasive testing performed on chromosomal microarrays, a method that is increasingly being adopted as a first-tier approach following a large NIH-sponsored study that published its findings last year (BAN 12/11/2012).
In comparison, when CellScape launches Clarity in the second half of 2014, it expects to be able to detect the "top microdeletion syndromes" that target between 20 and 40 regions , in addition to "most defects that are between 5 and 10 megabases in size or larger," Drexler said.
This will include "all the whole chromosome anomalies such as the trisomies of chromosomes 13, 18, [and] 21 as well as most of what can be resolved with a karyotype," she said. "We are looking for defects across the whole genome," Drexler added. "We will see between 5- and 10-megabase resolution across most of the regions but in our 20 to 40 targeted regions we will be able to see smaller defects."
Drexler portrayed Clarity as offering a higher-resolution look at the genome of an invasively-obtained sample than conventional karyotype, but being lower in resolution than the chromosomal arrays currently used in invasive prenatal testing, because of the "small number of cells" that CellScape uses as input.
The scope of the Clarity test may broaden in the future though. CellScape believes its "performance on arrays will improve over time" and that the company will "continually evaluate options for improving resolution and scope," Drexler said. She also noted that the firm aims to introduce sequencing-based tests for single-cell disorders, such as Tay Sachs disease and sickle cell disease next year.
"Our goal is to use the best available genetic analysis technique at the time for the type of defect we want to be able to identify," said Drexler.
Privately held CellScape is based in Newark, Calif. While arrays are at the core of its offering, its main technology expertise is in the isolation of fetal cells with viable DNA, Drexler said. On its website, the company markets Clarity, which is currently available for investigational use, as being able to provide a result to a pregnant woman as early as nine weeks into her pregnancy, providing the "benefits of invasive procedures such as amniocentesis or [chorionic villi sampling] without risk to the fetus or discomfort to the mother."
While Drexler did not provide additional information about the way the Clarity test works, she said that the company uses and expects to continue to use "fairly standard protocols for genetic analysis," as "this is not the part of the process where we are focused on invention."
She also denied that the company is using Agilent's protocol for single-cell comparative genomic hybridization, or some modification of that protocol, in its test. Agilent's protocol has been publicly available for over a year (BAN 7/3/2012).
In April, the US Patent and Trademark Office awarded CellScape US Patent No. 8,426,122, "Method and device for identification of nucleated red blood cells from a maternal blood sample." The patent describes a method of enriching for fetal nucleated cells from a maternal blood sample by passing the sample containing maternal and fetal nucleated cells through a leukocyte depletion filter; retaining nucleated cells including leukocytes on the filter; and eluting nucleated cells from the filter with an elution buffer, where the nucleated cells include fetal nucleated cells.
In order to offer Clarity as a clinical test, CellScape is working toward having its laboratory CLIA certified sometime prior to the launch of the test next year.
Drexler estimated the potential market size for Clarity to be all 4 million live births annually in the US. CellScape will first market the test as a screen and recommend that any findings be confirmed by invasive testing. As more data is generated, though, Clarity has the potential to become a diagnostic test, she said.