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Making their mark
SAN DIEGOŚNew England Biolabs Inc. (NEB) and Sequenom Inc. have signed a licensing and co-marketing agreement to commercialize research tools for epigenetics.
The companies have a longstanding relationship going back to 2005, notes Dr. Karsten Schmidt, vice president of business development at Sequenom. The two companies are currently developing plans to co-market each other's product offerings in the field of epigenetics, as NEB and Sequenom's products, such as EpiTYPER, are complementary in epigenetic research.
One early result of their research collaboration is the development of the EpiMark Methylated DNA Enrichment Kit from NEB. The kit utilizes the innovative proprietary technology and intellectual property, methyl-CpG-immunoprecipitation (MCIp), acquired by Sequenom through an assignment of intellectual property rights from the University of Regensburg in Germany. The MCIp technology is based on the work of Prof. Michael Rehli in the university's Department of Hematology and Oncology. It is used to advance discovery and analysis of differentially methylated regions in biological samples, such as methylation differences between fetal and maternal chromosomes that can enable non-invasive prenatal diagnostics.
In biology, and specifically genetics, epigenetics is the study of heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence. In earlier writings, Karsten has pondered the definition of epigenetics and its role in inheritance.
"Epigenetics takes care of the fact that chromatin (which consists half of proteins), and not just naked DNA, represents the physiological template for transcription, replication, recombination and DNA repair and also constitutes the actual heritable material being passed on to the daughter cells during mitosis and meiosis," he noted in a 2007 article. "Notwithstanding the ongoing efforts to find an accurate classification for this young discipline, the practical definitions recently provided by Peter Jones have shaped up as the most popular so far: epigenetics describes the "somatically heritable states of gene expression that are not coded in the DNA sequence itself" (emphasis his).
"Methylated CpG DNA is the hallmark of Epigenetics in higher organisms (vertebrates including humans)," Karsten states. "It is methylation of the cytosine base in specific places in DNA of higher organisms, which plays a critical role, particularly in developmental and reproductive biology and cancer. Thus, DNA methylation is a crucial part of normal organismal development and cellular differentiation in higher organisms. DNA methylation stably alters the gene expression pattern in cells such that cells can 'remember where they have been' or decrease gene expression; for example, cells programmed to be pancreatic islets during embryonic development remain pancreatic islets throughout the life of the organism, without continuing signals telling them that they need to remain islets."
The new methylated DNA enrichment kit incorporates the methyl-CpG binding domain of human MBD2, fused to the Fc tail of human IgG1. When coupled to magnetic beads, this antibody-like protein enables purification of methylated CpG DNA with superior sensitivity, accuracy and speed. NEB has enabled and optimized large-scale, high-purity manufacturing of the protein and developed a user-friendly kit for the research community.
"Collaborations have always played an essential role in the development of innovative research tools at New England Biolabs," states Dr. Salvatore Russello, associate director of business development at NEB. "This collaboration has been of great value to NEB and has facilitated the development of a novel tool to drive the discovery of epigenetic markers, an exciting new area of basic and applied research."
NEB will also be Sequenom's first-choice supplier if the technology should be used for prenatal diagnostic purposes in the future. Sequenom has retained all rights for diagnostic uses.
The EpiMark Methylated DNA Enrichment Kit is part of a suite of EpiMark validated products for epigenetics, which was launched by New England Biolabs at the American Association for Cancer Research 2011 Annual Meeting in April.