Researchers at the Tervisetehnoloogiate Arenduskeskus AS (Competence Centre on Health Technologies, CCHT) and the Karolinska Institutet have developed the patent-pending GlobinLock® technology (GL), which allows to analyse blood samples and gene expression profiles significantly faster and cheaper compared to alternative solutions. This novel technology could be an essential component of any blood-related molecular testing method.
Kaarel Krjutškov, the co-inventor of GlobinLock® told the story of the invention: “We needed to analyse blood samples from hundreds of asthmatic kids for a research project. Firstly, we did not have enough resources to use existing commercial solutions, and secondly, more importantly, the extremely limited amount of valuable blood-sample material from kids determined the need to develop something more economical. As a result, we invented the GlobinLock®, which is thirty times cheaper, ten times faster and needs only ten percent of a blood sample compared to other available solutions,” said Krjutškov.
Globin causes Analysing Difficulties
Blood sample analysis is widely used in clinical trials mainly due to its accessibility. In addition, blood is a valuable biopsy material that directly reflects the patient’s health condition. Blood contains a multitude of different cells types but most of them are erythrocytes, which transport oxygen. Because of that, 50–80% of RNA molecules extracted from the blood are globin RNAs and the RNA sample is “globin contaminated” in lab slang. “This complicates the laboratory analysis of blood samples, leaving biologically significant molecules of RNA undetectable,” explained Hardi Tamm, the marketing manager of CCHT.
“Blood samples are attractive to study but we need smart solutions to overcome specific challenges, e.g., globin,” noted Krjutškov and added that blood sample analysis without the elimination of abundant globin RNA is meaningless. The direct analysis of blood provides enormous amounts of repeating globin information and introduces a technical bias to the whole analysis procedure. However, this globin RNA locking tool is a robust and simple solution for blood origin transcriptome analysis. “The globin reduction rate of GL is enough for any application. It reduces the globin prevalence from 63% to 2% after GL treatment, which makes it an effective method for biotechnology companies as an additive to their blood analysis kits,” he explained.
Robust but Effective Tool
The GlobinLock® method consists of a pair of short synthetic DNA strands that silence the majority of globin RNA molecules with highly specific binding. The strands introduced to the purified RNA sample, are effective immediately after RNA denaturation and add only two minutes of analysis time to the whole laboratory procedure. The locking DNA molecules bind specifically at a globin RNA poly-A site that is critical for further analysis, silencing globin RNA selectively and leaving the rest of the molecules accessible. Therefore, the globin RNAs are “locked” prior to downstream manipulations and are unavailable to cause technical biases in blood RNA biomarker applications.
Similar to fuel prices in a gas station, genetic testing as a product has its selling price, which includes components like the procedure for blood collection, RNA extraction from blood, next generation sequencing, and data interpretation by skilled staff.
To bring an example: the cost price of transcriptome analysis is 50–200 euros (depending on the analysis method). The required elimination of globin would add extra 30 euros when a competitive method would be used, while applying GlobinLock® would add less than an euro to the analysis price.
Many Blood Samples waiting for Analysis
Hardi Tamm said that the method could speed up the transition of data-intensive applications from research to medicine because the price reduction could widen the capacities of blood-related research and increase the amount of useful data.
He noted that biobanks all over the world have already gathered millions of valuable samples and more are yet to come but not all planned analyses are made because of the budget. Implementing new knowledge in medical applications is even more important than a balanced budget. A new and cheaper method would help to do more analyses, open new avenues of discovery to find causative genes and biomarkers, and contribute to progress.
“This material would give us so much to observe—different diseases and the phases thereof, syndromes, stress, recovery after physical exercise, etc.—all that admirable information that blood with its RNA carries,” Tamm stated. He added that for meeting those challenges, they need to measure tens or hundreds of biomarkers simultaneously, which is where the GL’s contribution to reducing analysis time and cost cutting comes in.
“A wider spectrum of biomarkers could help to assess the state of patients more accurately, including in such complicated cases as the development of asthma, epilepsy or even depression. Doctors could choose the best treatment for different conditions and give patients more accurate instructions to stay healthy,” he said. Some opportunities RNA sequencing provides are already in medical use in cancer diagnostics and treatment. For example, in breast cancer, recent clinical guidelines support the use of multigene mRNA-based prognostic assays to assist in treatment decisions in conjunction with clinicopathological factors.
A Coup for Personal Medicine and Science
The opportunities of developing personal medicine in Estonia are wider than only the available infrastructure and e-solutions can provide. Patent pending GlobinLock® is an outstanding example of how a relatively small scientific community’s inventions contribute to personal medicine worldwide, making further research and diagnostics affordable.
Breakthrough technologies like GL support further investments as well as research made in Estonia through patents and trademark protection. “Balancing the high direct costs of diagnostics starts from surprisingly small details,” stated Krjutškov and added that a price reduction of ten to thirty per cent is only a cosmetic change but the real innovation starts when they can cut the price of the analyses by three or more times.
The great potential has also been noticed by others: GlobinLock®, an outstanding collaboration project between a research institution and the private sector that succeeded in an extremely short time, was honoured with the title of the technological innovation of the year at the Swedish Business Awards 2016 ceremony.
Byron, S.A., Van Keuren-Jensen, K.R., Engelthaler, D.M., Carpten, J.D., Craig, D.W. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. (2016) Nature Reviews Genetics 7, 257–271 doi:10.1038/nrg.2016.10
GlobinLock® was honoured as technological innovation of the year (2016) URL: http://ccht.ee/index.php/uudised/globinlock-was-honored-as-technological-innovation-of-the-year.
During 01.09.2015 – 31.08.2022 CCHT research and development activities are co-funded by the European Regional Development Fund project EU48695.
This article was funded by the European Regional Development Fund through Estonian Research Council.