The traditional wisdom passed down in biology textbooks is that DNA is neatly packaged in chromosomes within the cell nucleus, serving as a template for protein synthesis or cell replication. However, scientists have known for nearly half a century that DNA is also present outside of cells. Researchers have developed several public health applications for cell-free DNA. Unfortunately, these have previously been limited by cumbersome laboratory methods. In this blog, we’ll explore cell-free DNA and the impact that harvesting can have on public health research.
What Is Cell-Free DNA?
Cell-free DNA is just what it sounds like: DNA that is outside its traditional home in the nucleus of a cell. Blood, serum and plasma contain free-floating DNA that can be extracted and quantified. Some evidence suggests that this cell-free DNA is a consequence of cell apoptosis. This DNA may serve as a biomarker for certain diseases, making it important to harvest uncontaminated samples of cell-free DNA.
Public Health Impact of Harvesting Cell-Free DNA
The use of cell-free DNA has garnered considerable attention over the past decade as researchers have uncovered potential uses of the DNA. One prominent application of cell-free DNA is its use as a non-invasive test for a range of fetal abnormalities. Maternal plasma contains freely circulating cell-free fetal DNA. Use of this DNA has been proposed as a non-invasive way to test for genetic conditions without the risks associated with amniocentesis.
Another promising avenue for the use of cell-free DNA is in cancer patients. The blood of cancer patients contains elevated levels of tumor-derived cell-free DNA. The ability to extract this DNA could be useful for diagnosis and development of sensitive clinical prognostic indicators.
Unfortunately, prior technological limitations required cell-free DNA to be extracted immediately after sample acquisition due to concerns about contamination with genomic DNA. For facilities lacking the ability to separate plasma and cryopreserve samples, this presents a significant barrier to the ability to use cell-free DNA for diagnostic or prognostic purposes.
Approaches to Harvesting Cell-Free DNA
One of the challenges in harvesting cell-free DNA is avoiding genomic DNA that may contaminate the sample. For example, in pregnant women, less than 10% of cell-free DNA is fetal in origin. Thus, limiting cross-contamination with genomic DNA is essential to obtaining accurate results when using fetal cell-free DNA.
In a recent paper published in Clinical Biochemistry, researchers sought to create a method of preventing the release of genomic DNA into cell-free DNA samples. In most situations of genomic DNA contamination, the origin of the genomic DNA contaminant is white blood cells. Typical sample storage and shipping procedures agitate the samples, leading to nucleated cell disruption. This results in release of genomic DNA from the nuclei of white blood cells, contaminating the sample of cell-free DNA.
To reduce genomic DNA release, the scientists employed a reagent to stabilize white blood cells following a standard blood draw. They found that compared to typical blood collection tubes, tubes with the reagent had stable cell-free DNA and genomic DNA after one week. Even after 14 days, genomic DNA had increased only twofold in the special blood tubes, compared to a 456-fold increase in typical tubes. Shipping did not affect the proliferation of genomic DNA in samples, suggesting that this is an effective method to deploy in laboratory settings. Extending this technology may transform laboratory work and public health applications for cell-free DNA.
Impact of Harvesting Cell-Free DNA on Laboratory Work
With the advent of new reagents and technologies, the ability to harvest cell-free DNA is easier than before. Users may use the stabilizing reagent to collect blood samples without risk of contamination by nucleic DNA. This is a significant step forward that makes it much more clear-cut for clinical lab technicians to handle cell-free DNA samples.
Traditional methods of harvesting cell-free DNA required laboratory technicians to immediately process blood samples to extract and cryopreserve plasma. With the advent of cell-free DNA harvesting services, there is no need to extract plasma from blood. Furthermore, samples need not be frozen before being shipped to the laboratory for DNA extraction. Simply using a straightforward blood collection tube with a special reagent ensures the quality of cell-free DNA in the sample. The risk of contamination is low, shipping and handling samples is easy, and the quality of results is unparalleled.
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