"This new study addresses a problem that has been puzzling investigators in the field of noninvasive prenatal diagnosis over the last ten years," stated Dennis Lo, M.D. Ph.D., study co-author and Li Ka Shing Professor of Medicine at The Chinese University of Hong Kong. "Digital PCR technologies have enabled us to measure the minute imbalance of mutant and normal DNA sequences in maternal plasma. This has freed us from the past restriction for monogenic disease analysis where we could only look at the paternally-inherited mutations noninvasively. This research represents a significant paradigm shift in the way we approach plasma DNA-based diagnostics, and offers substantial promise for bringing noninvasive prenatal diagnosis of monogenic diseases closer to reality."

Data from the collaborative project show for the first time that when individual mutant or normal DNA sequences are counted in maternal plasma using digital PCR technology, the number of mutant genes inherited by an unborn fetus, and hence its disease status, can be determined. The authors further demonstrated that a 'molecular counting' strategy can be made more efficient by taking into account the length of the DNA molecules in maternal plasma, as fetal DNA molecules are known to typically be shorter than the maternally derived molecules in maternal plasma. Through the use of this digital counting approach, the authors were able to noninvasively diagnose B-thalassemia and hemoglobin E disease from maternal plasma - forms of inherited anemia that affect millions of people worldwide. This molecular counting strategy can in principle be applicable to all forms of monogenic diseases, namely paternally or maternally inherited autosomal dominant diseases and autosomal recessive diseases with any combination of parental mutations. Thus, the complete diagnosis of monogenic diseases can be achieved noninvasively.

"Sequenom is committed to developing the next-generation of prenatal diagnostic tools that will provide physicians with the capabilities they need to noninvasively diagnose genetic disorders early in a woman's pregnancy," said Harry Stylli, Ph.D., President and Chief Executive Officer of Sequenom. "Dr. Lo and his team have made another important breakthrough in prenatal diagnostics with these findings. These unique, noninvasive digital technologies have the potential to dramatically impact the prenatal diagnostic market and we look forward to continuing to work with Dr. Lo and his team to advance these innovative approaches as part of our long-term strategy to expand our prenatal diagnostics franchise."

The study, entitled "Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma" by Lun et. al., is available online in this week's Early Edition of PNAS at www.PNAS.org.

Monogenic Recessive Diseases

According to the World Health Organization, monogenic diseases result from modifications in a single gene occurring in all cells of the body. Though relatively rare for each disease, together they affect millions of people worldwide. Monogenic diseases are responsible for a heavy loss of lives. The global prevalence of all single gene diseases at birth is approximately 10/1,000. Scientists currently estimate that over 10,000 of human diseases are known to be monogenic. Pure genetic diseases are caused by a single error in a single gene in the human DNA. The nature of disease depends on the functions performed by the modified gene. The single-gene or monogenic diseases can be classified into three main categories: dominant, recessive, and X-linked.

All human beings have two sets or copies of each gene called alleles; one copy on each chromosome pair. Recessive diseases are monogenic disorders that occur from an individual having inherited two defective copies or alleles. Dominant diseases are monogenic disorders that involve defects to only one gene copy.

Prenatal diagnosis of monogenic diseases is currently performed by invasive procedures such as amniocentesis and chorionic villus sampling (CVS) which carry a risk of fetal miscarriage. The discovery of cell-free fetal DNA in maternal plasma offers noninvasive prenatal diagnostics which eliminate the risk to the fetus. For many monogenic diseases of medical interest, a different quantitative approach is needed. For example, for monogenic recessive diseases like cystic fibrosis and B-thalassemia, the fetus would need to have inherited two copies of the mutant gene to suffer from the disease. The inheritance of only one mutant gene signifies a disease carrier while inheritance of no mutant gene (or in other words, having inherited two normal genes) indicates a healthy fetus. However, such a precise degree of mutation quantification for noninvasive prenatal diagnosis has not previously been possible due to the presence of a high background of maternal DNA interfering with the analysis of the small amount of circulating fetal DNA in maternal plasma.

Sequenom's Proprietary Noninvasive Prenatal Diagnostics

Sequenom's commercial opportunities in prenatal diagnostics are built upon its SEQureDx(TM) technologies and are enabled by the pioneering inventions and associated intellectual property rights that it has exclusively licensed from Isis Innovation Ltd., the technology transfer company of the University of Oxford, as well as The Chinese University of Hong Kong. Sequenom's portfolio of noninvasive prenatal diagnostic patent rights and patent applications is platform-independent, includes genetic-analysis methods using circulating cell-free fetal nucleic acids from maternal serum, plasma or whole blood, and also includes a portfolio of methylation and nucleic-acid markers. Sequenom holds exclusive rights in territories including the United States, Europe, Australia, Canada, Japan and Hong Kong. Sequenom is actively expanding its intellectual property position with new technology and new territories. Because Sequenom's license rights are platform-independent, the rights provide exclusivity (with the narrow exception in Europe for RT-PCR-based Rhesus D tests) for development and commercialization of noninvasive prenatal screens and tests on any platform and are not limited to the Company's MassARRAY(R) platform.

About Sequenom

Sequenom is committed to providing the best genetic analysis products that translate the results of genomic science into solutions for noninvasive prenatal diagnostics, biomedical research, translational research and molecular medicine applications. The Company's proprietary MassARRAY system is a high-performance (in speed, accuracy and cost efficiency) nucleic acid analysis platform that quantitatively and precisely measures genetic target material and variations. The Company has exclusively licensed intellectual property rights for the development and commercialization of noninvasive prenatal genetic tests for use with the MassARRAY system and other platforms. For more information on Sequenom, please visit the Company's Web site at www.sequenom.com.

Sequenom(R), MassARRAY(R) and SEQureDx(TM) are trademarks of Sequenom, Inc.

About The Chinese University of Hong Kong

Founded in 1963, The Chinese University of Hong Kong (CUHK) is a forward looking comprehensive research university with a global vision and a mission to combine tradition with modernity, and to bring together China and the West. CUHK teachers and students hail from all corners of the world. In 2007, CUHK had more than 6,100 staff members, approximately 10,000 undergraduate and 3,300 research postgraduate students. Of these students, some 2,500 are from 45 countries and regions outside Hong Kong. The University received research funding of close to HK$400 million in the 2006/07 academic year from various local and overseas sources. Four research areas led by CUHK staff have been selected as four of only ten Areas of Excellence funded by the University Grants Committee. CUHK research centers have close collaboration with mainland China and overseas institutions. Many research products have been put into practical use through technology transfer and spin-off companies. Technology transfer at CUHK is handled by the Technology Licensing Office headed by Ms. Alice Ngan.

Forward-Looking Statements

Except for the historical information contained herein, the matters set forth in this press release, including statements regarding the potential of and opportunities associated with the new approach for noninvasively diagnosing monogenetic diseases, the next-generation of prenatal diagnostic tools, the impact of unique noninvasive digital technologies on the prenatal diagnostic market, the Company's long-term strategy to expand its prenatal diagnostics franchise, and the Company's commercial opportunities in prenatal diagnostics, are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the risks and uncertainties associated with the Company's operating performance, demand for and market acceptance of the Company's products, services, and technologies, new technology and product development and commercialization particularly for new technologies such as molecular diagnostics, and particularly noninvasive prenatal diagnostics, reliance upon the collaborative efforts of other parties, research and development progress, competition, intellectual property protection, government regulation, obtaining or maintaining regulatory approvals, and other risks detailed from time to time in the Company's SEC (U.S. Securities and Exchange Commission) filings, including the Company's Annual Report on Form 10-K for the year ended December 31, 2007 and other documents subsequently filed with or furnished to the SEC. These forward-looking statements are based on current information that may change and you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and the Company undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.

SOURCE: Sequenom, Inc.