The term “DNA plasma” can be a source of confusion as it is not a standard scientific term. It points to one of two distinct concepts in biology depending on the context. The first involves plasmids, which are small, circular DNA molecules in bacteria used in biotechnology. The second concept is cell-free DNA, which are fragments of DNA circulating in blood plasma and are a focus of modern medical diagnostics.
Plasmid DNA in Bacteria
In bacteria, small, circular, double-stranded DNA molecules called plasmids exist separately from the main bacterial chromosome. Plasmids are extrachromosomal, meaning they are physically distinct from chromosomal DNA and can replicate on their own. This independent replication is possible because they contain their own starting point for DNA duplication, a sequence known as an origin of replication.
Plasmids vary significantly in size and carry accessory genes. These genes are not required for the bacterium’s day-to-day survival under ideal conditions but provide a major advantage in stressful environments. For instance, many plasmids carry genes that confer resistance to one or more antibiotics. When a bacterium with such a plasmid is exposed to that antibiotic, it can survive while others without the plasmid perish.
This ability makes plasmids a factor in the spread of antibiotic resistance. Bacteria can transfer plasmids to one another through a process called conjugation, allowing advantageous traits to move horizontally through a population. Other plasmid-borne genes can help bacteria metabolize unusual nutrients, resist heavy metal toxicity, or produce toxins that help them colonize a host.
Using Plasmids as Biological Tools
Scientists have repurposed the natural properties of plasmids, transforming them into tools for genetic engineering and biotechnology. In the laboratory, plasmids are used as “vectors,” which are vehicles designed to carry a specific piece of foreign DNA into a host cell, typically bacteria like E. coli. This process allows for the production of vast quantities of a specific gene or the protein it codes for.
The process begins with an engineered plasmid vector that has features to simplify the procedure, like a multiple cloning site. This site contains several restriction enzyme recognition sites, which act as specific points where the plasmid can be cut open. Using these molecular scissors, scientists open the circular plasmid and insert a gene of interest, creating what is known as a recombinant DNA molecule.
Once created, these modified plasmids are introduced into host bacteria through a process called transformation. The vector also carries a selectable marker, most commonly a gene for antibiotic resistance, to identify the bacteria that have successfully taken up the plasmid. When the bacteria are grown in a medium containing that antibiotic, only the ones containing the plasmid will survive and multiply, becoming microscopic factories for the desired protein.
Cell-Free DNA in the Bloodstream
Shifting from the microbial world to human biology, the second interpretation of “DNA plasma” relates to cell-free DNA (cfDNA). This consists of small fragments of DNA that are not contained within cells but circulate freely in the bloodstream, specifically in the plasma, which is the liquid portion of blood.
The primary source of cfDNA is the natural process of cell death that occurs constantly throughout the body. As cells undergo programmed cell death (apoptosis) or die due to injury (necrosis), they break apart and release their DNA fragments into circulation. In healthy individuals, this process results in a low baseline concentration of cfDNA, and these fragments are generally small, with an average size around 166 base pairs.
This circulating DNA is a composite snapshot of cell turnover from across the entire body. Because cfDNA carries the genetic information of its cell of origin, its analysis can provide a window into the health of different tissues. For example, elevated levels of cfDNA or the presence of DNA with specific mutations can indicate an abnormal process, such as tissue damage, inflammation, or cancer.
Medical Applications of Cell-Free DNA
The ability to detect and analyze cfDNA from a simple blood sample has led to diagnostic tests, often referred to as liquid biopsies. These tests avoid the need for more invasive tissue biopsies and have found major applications in prenatal care and oncology.
One of the most established uses of cfDNA is in Non-Invasive Prenatal Testing (NIPT). During pregnancy, a fraction of the cfDNA in an expectant mother’s bloodstream originates from the placenta. This placental DNA is usually genetically identical to that of the fetus and can be analyzed to screen for certain chromosomal abnormalities. NIPT can detect conditions like Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13) with high accuracy.
In oncology, the analysis of cfDNA has opened new frontiers for cancer detection and management. Tumors shed DNA fragments, known as circulating tumor DNA (ctDNA), into the bloodstream. Detecting ctDNA can help in several ways: it can serve as a biomarker for early cancer detection, help profile the specific mutations in a tumor to guide targeted therapy, and monitor a patient’s response to treatment or check for disease recurrence. This approach is valuable for tracking cancers that are difficult to biopsy or for getting a more comprehensive picture of metastatic disease.