Keener than ever to establish itself as a key genomic research tools provider for in vitro fertilization laboratories, BlueGnome recently rolled out a new offering designed to help doctors better understand the biological factors underlying recurrent miscarriage.
Called 24sure+, the approach complements the Cambridge, UK-based firm's 24sure offering, launched last year (BAN 9/8/2009), which uses a bacterial artificial chromosome array and software to screen for abnormal or aneuploid chromosomes during an IVF cycle.
By comparison, 24sure+ has "much greater coverage than 24sure," and allows users to detect smaller chromosomal imbalances, Graham Snudden, vice president of engineering, told BioArray News this week.
According to Snudden, this expanded capability is useful for studying recurrent miscarriage, which is often linked to the presence of balanced translocations in one or both parents. As there is no net gain or loss of genetic material in a balanced translocation, carriers are normal.
However, the underlying aberration can lead to structural imbalances in an embryo, where there is a gain or loss. Such embryos are seldom viable and frequently end in miscarriage, he said.
Snudden noted that BlueGnome is planning other kits for the IVF research market. "We have a number of active R&D projects which are being undertaken in collaboration with thought leaders … from around the world," he said. "Our aim is to use our unique combination of array technology and signal processing expertise to deliver a complete suite of products for research into pre-implantation genetic screening and diagnosis."
Fluorescence in situ hybridization is currently used by those carrying out pre-implantation genetic investigations to select balanced embryos for IVF. According to Snudden, though, such assays are "time consuming, expensive to work up, and technically difficult to use for screening of all the possible imbalances that can be predicted from a parental translocation."
BlueGnome is now positioning 24sure+ as a complement to FISH. 24sure is used to screen for aneuploidy, a source of infertility, by confirming that eggs and embryos contain the correct number of chromosomes. In comparison, 24sure+ has been optimized to investigate imbalances affecting only part of a chromosome since small imbalances are commonly found to result from translocations.
"24sure+ enables research into a completely new indication — recurrent miscarriage — where the balanced translocations in one or both parents are believed to result in large-scale structural abnormalities in the embryo," Snudden said. "The problem here is not failure to establish the pregnancy but failure to bring it to term."
According to Snudden, 24sure+ offers "greater resolution" than 24sure. "The analysis is also much more sophisticated as laboratories need to predict the probability of detecting the derived chromosome fragments that can themselves be predicted from the cytogenetics of the parents," Snudden said.
"By combining our knowledge of the clone positions with performance of the assay, we are able to help laboratories understand, in advance of the test, whether all the derived chromosomes will be detected and whether 24sure+ will be appropriate for the investigation," he added.
In a recent statement, BlueGnome CEO Nick Haan said the launch of 24sure+ "highlights research interaction between classical cytogenetic laboratories and their IVF counterparts."
Cytogenetics laboratories "play a key role" by characterizing balanced translocations in parental DNA, Haan noted. This information is then used by IVF laboratories "using increasingly sophisticated cytogenetic methods" to investigate imbalances pre-implantation.
Haan said that the use of BlueGnome's technologies by Italian IVF lab Genoma in both traditional cytogenetics and IVF is a "powerful example of this technology crossover."
Francesco Fiorentino, who has been using 24sure+ in his Rome-based lab to achieve successful pregnancies in couples that were previously affected by recurrent miscarriage, in a statement called 24sure+ a "very powerful technique" that also has the "potential to assess aneuploidies for patients of advanced maternal age, overcoming the limitation" of FISH-based procedures.
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According to Snudden, Genoma is one of more than 50 IVF labs that use 24sure products for pre-implantation research. He expects "most of them to use 24sure+ to further our understanding of this very important area of infertility."
Most of BlueGnome's 24sure products are sold as kits to its clients. 24sure+ will also be available as a service through its spinoff Sure Laboratories. Established earlier this year, Sure Labs, also based in Cambridge, is an independent clinical cytogenetics services company dedicated to serving the market for pre-implantation genetic-screening services (BAN 9/7/2010).
Founded in 2001, BlueGnome began its activities in the IVF research market just last year. To date, the firm has specialized in products and services for use in cytogenetics research, including BAC and oligonucleotide versions of its CytoChip for characterization of chromosomal imbalances, with specific CytoChips available for constitutional and hematology studies.
The firm also sells BlueFISH probes and BlueFuse software designed to analyze comparative genomic hybridization and expression-profiling data.
In addition to founding Sure Labs, the firm in October acquired the IP to a method called karyomapping from inventor Alan Handyside and the London Bridge Fertility, Gynaecology, and Genetics Centre, where Handyside is the scientific director. As part of the deal, Handyside joined BlueGnome as head scientist of pre-implantation genetics (BAN 10/19/2010).
Karyomapping relies on the ability to obtain SNP-genotype information from relatives, such as parents and grandparents, as well as those who are known to carry a deleterious gene. By matching the SNP genotypes of embryos to relatives, and knowing where the deleterious gene resides, it is possible to infer the status of the embryo, according to BlueGnome.
The firm's ultimate goal is to enable firms to screen for single-gene conditions using the approach. It has not provided a timeline for when the new product will become available.
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