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Mar 15, 2009 (Vol. 29, No. 6)

miRNA Profiling Opens Doors for New Drugs

Researchers Are Working to Understand Its Role and the Cellular Pathways It Affects

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    Many key biological processes are impacted by miRNAs, including cell growth and proliferation, tissue differentiation, embryonic development, and apoptosis. Mutation, dysfunction, and/or dysregulation of miRNA may lead to diseases like coronary artery disease, cancer, diabetes, AIDS, hepatitis, and obesity, to name a few.

    Many companies are excited about the potential of miRNAs and are developing novel methods to profile these small RNA molecules and understand which cellular pathways they affect. Later this month, the researchers profiled in this article will be presenting their latest findings at CHI’s “microRNA in Human Disease and Development,” to be held in Boston.  

    Recent statistics from the National Center for Health Statistics estimate that 34% of U.S. adults are obese. Understanding the role of miRNAs in adipose biology may lead to novel RNA-based therapies for obesity.

    Harvey Lodish, Ph.D., professor of biology and bioengineering at MIT, along with graduate student HuangMing Xie, has been profiling and validating the expression of more than 370 miRNAs during adipogenesis of various fat cells. “I’ve been studying fat cells for the past 25 years in various contexts,” states Dr. Lodish. “The hope for this project was that we could find microRNAs that were induced during adipose development that could play some important roles in the biology of cells.”

    A number of miRNAs have been discovered that are induced during fat development: two miRNAs upregulated actually sped up the rate at which fat cells are formed by a day, which is substantial. The researchers also compared fat tissue from obese animals versus normal animals.

    “What we found very striking is that the same miRNAs that were normally turned on during fat cell differentiation were at a lower level than fat cells from obese animals versus the normal animals.” He concludes that these miRNAs are playing key roles in regulating fat-cell formation. “We’re getting lineage-specific miRNAs that affect the differentiation pathway, making this the first time it’s been done in fat cells.”

  • Microfluidic Chip Advances Research

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    A flexible microfluidic array platform, designed with an advanced biochip, is enabling miRNA research, according to LC Sciences. The firm’s µParaflo® chip allows for miRBase synchronicity and design of custom biochips. Although the chip was developed about eight years ago, the company focused on the miRNA market in 2005. The microfluidic technology produces a uniform distribution of the sample solutions on the array and enhances binding reactions and stringency wash processes, says Christoph Eicken, Ph.D., head of technical services, microarrays.

    An advanced manufacturing process ensures uniform spots and high reproducibility across lots of arrays and also permits total customization of contents on each individual array. “We have special chemistry where we use regular building blocks to synthesize Tm-optimized probes —meaning we don’t have to use modified oligos or modified amino acids for protein arrays,” explains Dr. Eicken.

    “The synthesis that we developed enabled us to use standard oligo-building blocks. We space chemically modified oligos along each of the probes in order to modify those Tm. We feel that’s really important in order to achieve uniform binding,” states Chris Hebel, director of business development. He adds that most of their customers are not microarray experts, and they usually have a few samples of disease versus normal state and want to know if the microRNA is up- or downregulated. “For them, it’s easy to send off the samples and we send them the data. There’s a time savings—it takes about three months after buying a chip to figure out the protocol and to get it to work.”

    The company also provides coverage of the latest miRNA sequence information from the Sanger miRBase sequence database.

    Future applications include complementary use with sequencing technologies. “Our technology is suited for capturing a portion of a sample, DNA, or RNA, and sequencing a targeting region of that sample. One way is the fact we can synthesize custom arrays with probes designed to capture whatever region of genome or scriptome is being analyzed.

    “The other way is that we can use the chip to synthesize probes, which can be cleaved off the array and used for in-solution capture. This is unique as well,” explains Hebel. 


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