Scientists are developing a new diagnostic tool for liquid biopsies

Areeba Khwaja

Researchers at UT-Austin are developing a new diagnostic tool for use in medical tests called liquid biopsies to detect cancers and other diseases.

The researchers are using an ancient bacterial enzyme, or a type of protein that can help carry out reactions in cells, that can analyze blood samples much more efficiently and accurately. Their new approach could be used for personalized medicine for patients and give doctors a more holistic picture of a patient’s disease and possibilities for future treatment.

“A liquid biopsy involves the analysis of small amounts of DNA or RNA that are released from tumors and other diseased tissues into the blood and bodily fluids,” said Alan Lambowitz, a molecular biosciences professor. “With a sensitive enough detection method, these small amounts of nucleic acids can be analyzed.”

Lambowitz said nucleic acids in the blood samples can be analyzed by DNA or RNA sequencing to find the locations of the mutations that could be causing disease and tissue damage.

Most current liquid biopsies can analyze DNA or limited amounts of RNA. However, the enzyme the researchers have studied can detect a much larger range of RNAs and with more accuracy. RNA is more beneficial for use in liquid biopsies because it provides a detailed snapshot of what’s happening inside of a cell at a particular time, said Lambowitz and Alfred Lentzsch, co-author of the study and graduate student of molecular biosciences.

“Cellular RNAs … can be used to monitor day-to-day progression of the disease, response to treatment and how different individuals with the same cancer will respond to different treatments,” Lambowitz said.

According to the researchers, liquid biopsies could potentially be used to diagnose and monitor a large variety of diseases including cancer, diabetes, neurodegenerative diseases, stroke, brain damage, rejection of organ transplants and infectious diseases.

“Because it requires a simple blood test, liquid biopsies make it possible to monitor disease progression and response to treatment on a daily basis,” Lambowitz said. “Liquid biopsies should be able to provide clinically actionable ‘yes or no’ answers within one day.”

Jennifer Stamos, a postdoctoral fellow, extensively studied the RNA-detecting enzyme used in this research. The enzyme is part of a group called TGIRTs — thermostable group II intron reverse transcriptases — which have a surprising combination of properties that are lacking in the enzymes currently often used in liquid biopsies, according to Stamos.

“We found that TGIRTs have novel activities that make it possible to efficiently and accurately sequence very small amounts of RNA present in the blood and detect classes of RNA that are not readily detected by other methods,” Lambowitz said.

The researchers said that in the future, they are looking forward to developing blood tests that could be used in conjunction with routine physical examinations for early detection of cancer and other diseases.

“Rather than requiring a specific test for each disease, all of the diagnostic information would be obtained in a single test based on the presence of different RNA biomarkers in blood,” Lambowitz said.

The researchers are also collaborating with other healthcare institutions in Texas to further develop liquid biopsies as diagnostic tools.

“We are currently working on developing … liquid biopsies for inflammatory breast cancer with physicians at MD Anderson and multiple myeloma with scientists at City of Hope,” Lambowitz said. “We hope to extend this work to many other diseases.”