Free-floating messages in the bloodstream could soon provide a unique window into the body. Researchers worldwide are racing to decipher circulating genetic material for better ways to diagnose disease, monitor pregnancy, and even improve food safety.
Circulating DNA and RNA—temporary gene copies that act as blueprints for protein production—was first discovered in 1948. Researchers still do not fully understand how the free-floating genetic fragments (chemically referred to as nucleic acids) survive outside the protective barriers of cells, but recent technological advances now allow scientists to comb through these tiny messages for clues about human health.
Traditional genetic screens, such as paternity tests and criminal profiling, utilize the abundant DNA stored in the nuclei of circulating blood cells. Although these tests shed light on a person's genetic inheritance, they do not provide insights on the current health of specific tissues and organs—information that could potentially be gleaned from the free nucleic acids.
Debate about the exact origins of circulating DNA and RNA continues, but dead cells from all areas of the body certainly contribute to the pool with new evidence mounting that living cells also release nucleic acids, perhaps enabling cell-to-cell communication over vast distances in the body, says Asif Butt, senior research fellow at King's College London.
Even healthy patients have circulating DNA and RNA, says Michael Fleischhacker, a molecular biologist at Charité-Universitätsmedizin Berlin hospital, but individuals with chronic disease such as cancer, inflammatory bowel disease and systemic lupus typically harbor increased levels of these messages in their blood. Simply monitoring the overall concentrations of nucleic acids in circulation, however, does not provide sufficient information about any one condition, prompting scientists to hunt for genetic targets specific to particular diseases.
Cancer researchers, for example, are seeking out patterns of chemical modifications and mutations detectable in the circulating gene fragments that are unique to malignancies. This approach could allow physicians to profile tumors without invasive sampling, says David Hoon, a molecular oncologist at the John Wayne Cancer Center Institute in Santa Monica, Calif.
The long-term goal is to identify genetic guides that can point physicians to a tumor's location as well as patterns that are characteristic of its stage to determine and monitor treatment and disease progression in patients, says Brian Durie, an oncologist at the Cedars–Sinai Medical Center's Samuel Oschin Comprehensive Cancer Institute in Los Angeles.
Fleischhacker cautions, however, that preparing these tests for routine cancer screening is likely to take a few years, because today's sensitive techniques can also detect rare mutations in healthy people that are of no clinical consequence.
Perhaps the most successful application of testing circulating DNA to date has been in the area of prenatal care. In the late 1990s researchers first recognized that fetal DNA could be detected in the mother's blood, albeit at very low levels, opening the door for noninvasive testing during pregnancy.
Traditional methods for examining fetal DNA, such as amniocentesis, require removing a sample of amniotic fluid surrounding the baby, increasing the risk of miscarriage, says Diana Bianchi, professor of pediatrics at Tufts University School of Medicine in Boston. Analysis of the mother's blood, on the other hand, could allow physicians to safely monitor the fetus and mother throughout the pregnancy.
In the U.S. and Europe, blood tests have already been approved for the diagnosis of rhesus D incompatibility—a condition in which a mother produces antibodies against her fetus due to the absence of the blood factor in her own body. Gender screening is also performed in Europe for families at high risk of passing on genetic disorders linked to the X chromosome. Bianchi says blood tests for Down's syndrome could be available in the near future.
Beyond cancer and prenatal testing, circulating nucleic acids could help physicians track a broad range of diseases, including stroke, heart attack and complications from diabetes. Butt's team has already identified several genetic markers important for diagnosing (and potentially predicting) diabetic retinopathy—damage to the eye's retina. Currently, only annual comprehensive eye tests can detect the condition, which is a leading cause of blindness in adults in the U.S., according to the National Eye Institute in Bethesda, Md.