Innovative technological advances could potentially provide clinical laboratories, pathology groups, and medical researchers with improved methodologies for designing, performing, and analyzing lab tests that use genetic information

Researchers at the University of Texas at Austin (UT Austin) have developed an innovative new enzyme that promises to improve the methods and tools used by pathology groups and clinical laboratories when conducting genetic testing.

The enzyme enables the reproduction of large quantities of Ribonucleic acid (RNA) to be accurately duplicated. It also can perform reverse transcription and scrutinize itself while copying genetic information, which will enable both researchers and clinical laboratories to improve the accuracy of gene sequencing where RNA is involved.

The team published their findings in Science, the academic journal of The American Association for the Advancement of Science (AAAS) and filed for a provisional patent for the new sequence of the discovered enzyme.

Strengthening Accuracy in Genetic Research

Biology Online defines reverse transcription as “the process of making a double stranded DNA molecule from a single stranded RNA template through the enzyme, reverse transcriptase.”

In reverse transcription, retroviruses can compel RNA to make copies of Deoxyribonucleic Acid (DNA). However, the process is widely known to produce errors. A 3-billion-year-old evolutionary ancestor of all viruses never formed the capability to precisely duplicate genetic material. The new discovery by the Texas researchers establishes a remedy for this problem.

“We created a new group of enzymes that can read the genetic information inside living cells with unprecedented accuracy,” said Jared Ellefson, PhD, Postdoctoral Researcher at UT Austin’s Center for Systems and Synthetic Biology (CSSB), in a ScienceDaily press release.  Ellefson was one of the authors of the study. “Overlooked by evolution, our enzyme can correct errors while copying RNA,” he concluded.

The researchers believe the breakthrough will strengthen accuracy in genetic research and could potentially improve medicine and enhance treatment therapies based on the genetic makeup of individuals.

Andy Ellington, PhD (above), Professor, Molecular Biosciences at UT Austin, co-authored the research paper, “Synthetic Evolutionary Origin of a Proofreading Reverse Transcriptase,” which was published in the AAAS journal Science. (Photo copyright: University of Texas at Austin.)

Andy Ellington, PhD (above), Professor, Molecular Biosciences at UT Austin, co-authored the research paper, “Synthetic Evolutionary Origin of a Proofreading Reverse Transcriptase,” which was published in the AAAS journal Science. (Photo copyright: University of Texas at Austin.)

“As we move towards an age of personalized medicine, where everyone’s transcripts will be read out almost as easily as taking a pulse, the accuracy of the sequence information will become increasingly important,” said Andy Ellington, PhD, Professor, Molecular Biosciences at UT Austin and co-author of the work, in the press release. “The significance of this is that we can now also copy large amounts of RNA information found in modern genomes, in the form of the RNA transcripts that encode almost every aspect of our physiology. This means that diagnoses made based on genomic information are far more likely to be accurate.”

Detecting Disease Earlier

Reverse transcription was discovered in the 1970’s and since then, it has been effectively utilized to enrich the understanding of genetic data in relation to hereditary diseases and elements of human health. It is primarily associated with retroviruses, however, the error-prone tendency of existing RNA sequencing has proven to be a dilemma for researchers and scientists.

A second new technology that incorporates fresh knowledge of RNA in ways that can improve how the data is used in clinical lab tests has been created by scientists in Switzerland.

Researchers from the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich in Basel have created a new way to record the genetic properties of antibodies in individuals. Prior to the development of this cutting-edge technology, the process of genetic sequencing had not been sophisticated enough to accurately distinguish antibody immune responses.

The new method, based on barcode genetics, conveys more information than the existing antibody detection methods and is more reliable and precise in its findings. The old method analyzed antibody proteins, whereas the new technique looks at a large quantity of messenger RNA molecules that instruct the body to generate antibodies.

It is estimated the human body contains several billion variations of antibodies. Unmasking their differences at the genetic level is difficult due to the high degree of precision required for the task. With the technique discovered, the D-BSSE researchers could ascertain how the human immune system creates antibodies following an infection or treatment like a vaccination.

By using distinctive genetic barcodes prior to amplification of the RNA and computer analysis, the researchers provided more accuracy by removing over 98% of errors in the sequencing data.

Antibody sequencing can now be an integral part of immunological research and may be used to develop new antibody drugs and vaccines.

“For example, our technique can be used to track precisely how an immune response changes over time, such as in human patients with an HIV infection,” explained Sai Reddy, PhD, in a ScienceDaily press release. Reddy is Professor of Biomolecular Engineering at ETH Zurich and leader of the study. “Previously, measurements of antibody proteins allowed scientists to discover primarily the very frequent antibodies. However, an immune response always yields a whole range of slightly different antibodies. Sequencing allows us to characterize even the rare ones very accurately and very quickly.”

Antibody sequencing may also be used to detect antibody molecules at an early stage, which may be extremely beneficial in the early detection of cancer and autoimmune diseases. Further advances in this type of research can vastly improve the outcomes of testing performed by pathology groups and clinical laboratories.

—JP Schlingman

Related Information:

Fix for 3-billion-year-old genetic error could dramatically improve genetic sequencing

Reverse Transcriptase