Oxford Gene Technology this week launched a new microarray that can be used to screen embryos for chromosomal abnormalities prior to implantation during an in vitro fertilization cycle.
The CytoSure Single Cell Aneuploidy oligonucleotide array detects such abnormalities, or aneuploidy, across all 24 human chromosomes using DNA amplified from a single cell from an early-stage embryo, OGT said, enabling the selection of an embryo with a normal chromosomal content, OGT said.
OGT's new market entry mirrors interest shown by Illumina, which last year purchased Cambridge, UK-based BlueGnome, a provider of a bacterial artificial chromosome array-based PGS offering called 24sure (BAN 9/25/2012). Illumina more recently acquired Verinata Health, a provider of next-generation sequencing-based non-invasive prenatal testing, as part of its larger push into the reproductive health market (BAN 5/14/2013).
James Clough, vice president of commercial activities at OGT, said that launching an array for the PGS market is a "natural progression" for the Oxford, UK-based firm, which already offers a menu of CytoSure arrays for constitutional and cancer cytogenetics testing.
"We have an established reputation in delivering class-leading products for constitutional analysis and we could see within the PGS market a clear and unmet need that could be addressed by a specifically designed and optimized oligo-based aCGH product," Clough told BioArray News this week. "While the PGS and broader reproductive health market is still in its relative infancy, we are predicting significant and rapid growth."
OGT's arrays are manufactured by Agilent Technologies.
OGT's most direct competitor in the nascent market is BlueGnome, which has been offering BAC arrays for PGS for years, and spun out a company called Sure Laboratories that specializes in array-based PGS (BAN 9/7/2010). While BlueGnome already has a customer base that includes fertility practices that offer IVF, such as the Genetics and IVF Institute and Pacific Reproductive Center, OGT seems to believe that its oligo arrays have a technical advantage over BAC arrays, as well as fluorescence in situ hybridization.
Describing OGT's new offering as the "first commercially available oligonucleotide aCGH offering designed specifically for PGS," Clough said that OGT's array is "sensitive enough to work with small amounts of amplified DNA from a single cell from an early-stage embryo."
Unlike FISH, OGT's chips can detect aneuploidies across the whole genome, he claimed. He also provided a number of reasons why OGT believes its offering is competitive with BlueGnome's BAC arrays. These include higher-throughput experiments, reduced sample-to-sample variation, higher resolution, and greater flexibility on content.
OGT's slides contain eight, 15,000-marker arrays, enabling eight samples to be processed on one slide, "which is more than existing bacterial artificial chromosome aneuploidy arrays," Clough claimed, adding that the ability to survey multiple samples on the same slide limits sample-to-sample variation by "reducing technical noise."
Likening the development of the array-based PGS market to the constitutional cytogenetics market, Clough predicted that in the future, customers will want to use tools that support higher-resolution analysis. "Unlike BAC arrays, which have limited resolution capabilities, oligo arrays are an ideally suited, future-proofed technology," said Clough.
The firm's arrays also allow "flexibility in content, which further enhances their utility to meet any future customer requirements," Clough added. He described the CytoSure Single Cell Aneuploidy array as the "first of a pipeline of new products for PGS from OGT that will be based on oligonucleotide aCGH technology." He said some of these products would be available by the end of the year, but declined to elaborate.
It is unclear if Illumina's BlueGnome, which sells Agilent-made oligo arrays for constitutional and cancer cytogenetic testing, will eventually launch an oligo array-based PGS product. Illumina CEO Jay Flatley told BioArray News recently that BlueGnome's future products would be developed on Illumina's BeadChip platform (BAN 5/21/2013).
According to Clough, OGT's oligo array-based PGS protocol involves the amplification of DNA obtained from either first polar bodies, single blastomeres, or trophectoderm biopsies using Rubicon Genomics' PicoPlex WGA Kit.
"The rest of the protocol follows the typical streamlined CytoSure aCGH workflow," Clough said. Analysis is performed using the firm's CytoSure Interpret Software, which enables the "clear identification" of aneuploidy, he claimed.
"The ability to clearly identify aneuploidy is vital to make a confident and informed decision as to the chromosomal content of an embryo," Clough said. He noted the array has also been research-validated to investigate aneuploidies in first polar bodies, single blastomeres, and trophectoderm biopsies at "two leading European facilities," which he did not name.
Clough said that one of the challenges when working with amplified DNA, especially when the starting amount is limited, is that not all of the genome is amplified equally.
To overcome this issue, OGT selected the probe content for its CytoSure Single Cell Aneuploidy array following "extensive testing" of DNA that has been amplified from single cells using the PicoPLEX WGA Kit, ensuring that the array content "mirrors the amplified genome," Clough said. He added that regions of the genome that are not amplified are not represented in the array content, "minimizing the possibility of obtaining misleading results."