Scientists at the Center for Genomic Regulation (CRG) in Barcelona developed a new tool that enables the use of transfer ribonucleic acid (tRNA) molecules as biomarkers for diagnose cancers and do so in the near future in less than three hours and at a cost of less than €50 per sample.

The creators of this innovation, who publish their work this Thursday in the journal ‘Nature Biotechnology’, managed to develop for the first time a method to measure tRNA abundance and modifications in a simple and inexpensive way, with promising applications for diagnose and predict disease, and that it is also not an invasive test and has high sensitivity and specificity.

The method was developed by Eva Novoa’s research group at the CRG in Barcelona and, with funding from the Spanish Association Against Cancer, is now are using the method as a basis to develop a new kit and a platform that will be able to determine whether a biological sample is carcinogenic and predict its malignancy in less than 3 hours and at the aforementioned cost.

As Novoa explained, when transfer ribonucleic acid (tRNA) molecules are incorrectly modified, they produce defective or incomplete proteins, which is associated with several human diseases, including neurodegenerative, metabolic and carcinogenic.

tRNAs are information-rich molecules with enormous potential for the diagnosis and prognosis of diseases, and until now they have not been explored due to the lack of methods that can capture this information in a quantitative and economical way”, said the researcher.

“Being able to isolate tRNA molecules from blood samples and quantify their modifications can help diagnose cancers without using imaging tests or invasive biopsies. In addition, the type of tRNA modification can change according to the state of the disease, providing valuable information”, Nova added.

Current methods for measuring tRNA molecules usually involve techniques such as next-generation sequencing or mass spectrometry, with limitations to diagnose because they cannot detect the modifications or are not able to identify where they are in the tRNA molecule.

This new method, called Nano-tRNAseq, according to the CRG scientists, it can measure both the abundance and modifications of tRNA molecules in a single step and is based on nanopore sequencing, a technology that can sequence RNA molecules directly by passing them through a small pore and detecting changes in the electrical current that is generated as each nucleotide passes through the pore.

Before we relied on two separate methods that are less informative, would take weeks and cost thousands of dollars to get results. Nano-tRNAseq is much cheaper and we can have results in a few days. In the near future, it will be in a few hours,” said CRG researcher Morghan Lucas.

Another advantage is that the nanopore sequencing machines for Nano-tRNAseq use are small, lightweight and can be powered by a laptop or external battery, making it easy to transport and use in the field or clinic.

Although there are still some limitations of the new method, which was tested with yeast tRNA, Lucas states “that the use of Nano-tRNAseq in parallel with other methods allows describing the modification profiles of the complete set of tRNAs in humans and, in the future, using Nano-tRNAseq to identify which changes in tRNAs are associated with a given disease.”

“Nano-tRNAseq is a proof-of-concept technology that paves the way to develop a simple, inexpensive and highly accurate method that can non-invasively quantify these molecules. Our goal is to further develop this technology and combine it with intelligence tools determine the malignancy of a biological sample in less than three hours and at a cost of no more than 50 euros per sample”, concluded Novoa