Project: Development and validation of a non-invasive prenatal diagnostic (NIPD) kit for aneuploidy detection
The CO purpose of this project is to develop and validate a non-invasive prenatal diagnostic (NIPD) kit for detection of the most common fetal chromosome aneuploidies. In contrast to conventional invasive testing methods that require fetal amniotic cells or chorionic villi, the NIPD kit will detect trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome) and fetal sex chromosome aneuploidies such as monosomy X (Turner syndrome) from a maternal peripheral blood sample._x000D_NIPD-based tests have been in development for over 10 years since the discovery of free fetal DNA (ffDNA) in maternal circulation during pregnancy. The impetus for such development stems from the increased risk (~1%) of miscarriage because of current invasive fetal sampling methods such as amniocentesis and chorionic villus sampling (CVS). However, the amount of ffDNA in maternal circulation is very low (~5-10%) and is inherently 50% similar to maternal DNA, which has raised significant technical challenges for its use in prenatal testing. Nevertheless, researchers have taken advantage of characteristics of ffDNA along with technological innovations to overcome these technical challenges and make NIPD testing for fetal abnormalities possible. The CO Participant of this proposal, NIPD Genetics, has patented a unique NIPD method to detect Down syndrome. The method uses a combination of methylated DNA immunoprecipitation (MeDIP) and real-time qPCR (RTqPCR) using DNA extracted from blood of pregnant women at 10-17 weeks gestation. Pivotal to the test was the identification of differentially methylated regions (DMRs) on chromosome 21 that are hypermethylated in the fetus and hypomethylated in the mother. Following MeDIP, which uses an antibody specific for methylated DNA, the resulting enriched methylated DNA is used for downstream RTqPCR amplification of these unique chromosome 21 regions. Statistical analysis of the RTqPCR data from multiple DMRs and control regions enables determination of copy number (e.g., 2 versus 3) and therefore, affected status (e.g., normal versus trisomy 21). Thus, the DNA methylation status of these DMRs are used to increase the available amount of fetal DNA sufficiently for diagnostic testing and as a means to discriminate fetal from maternal DNA._x000D__x000D_Building on NIPD Genetics’ position as the only European patent holder for a NIPD-based method for detecting fetal aneuploidies, the current ambitious goal is to commercially produce the first NIPD aneuploidy detection kit worldwide. This will be achieved by expanding the diagnostic scope of the current MeDIP-RTqPCR method to include all common fetal chromosome aneuploidies, to test and evaluate new technologies in MeDIP and RTqPCR to improve the NIPD method, and to validate the NIPD kit and ensure it meets all regulatory requirements needed for commercialization. Although NIPD Genetics is the only patent holder in Europe in a position to provide NIPD-based services, competitors in the United States have started to provide NIPD aneuploidy detection services using next-generation sequencing (NGS) based methods in the U.S. since last year. However, none of them have developed a kit version of their protocols focusing instead on the provision of services. Successful development and commercialization of a NIPD aneuploidy kit will be an industry first and will be based on the MeDIP-RTqPCR method which is unrelated to the NGS-based methods used by competitors in the U.S. It is anticipated that the new MeDIP technologies investigated for this product may also be used to commercialize a product for epigenetic-based research, and the Consortium is fully prepared to take advantage of the opportunity as well as any other intellectual property rights (IPR) that arise from the project._x000D__x000D_The Consortium of the proposed project consists of two highly experienced European R&D performing SMEs that have extensive expertise and research experience relevant to the project. NIPD Genetics is a leader in the field of non-invasive prenatal diagnosis and patent holder of a unique MeDIP-RTqPCR method for the detection of Down syndrome, and will be responsible for the development and testing of new technologies as well as the development and validation of the new NIPD kit. Diagenode is a leader in the field of epigenetics providing kits and equipment for chromatin immunoprecipitation and DNA methylation research. Together the Consortium will collaborate in developing new MeDIP-based technologies for use in the project’s NIPD kit and investigate development of a stand-alone MeDIP epigenetic research kit designed for low starting amounts of DNA from blood or plasma. Thus, while the CO goal of the project is to develop and commercialize a NIPD aneuploidy detection kit for diagnostic laboratories worldwide to safely and accurately diagnose fetal chromosomal abnormalities, new or improved epigenetic products for research use may also be produced.
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Acronym
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NIPD-KIT
(Reference Number: 8600)
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Duration
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01/11/2013 - 31/03/2016
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Project Topic
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The purpose of this project is to develop and validate a novel non-invasive prenatal diagnostic (NIPD) kit for the detection of aneuploidies on chromosomes 21, 18, 13, X and Y for use in genetic diagnostic laboratories worldwide.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 10
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Project partner
