Groundbreaking PCR technology to halt the spread of disease

The COVID-19 pandemic led to many changes. Among them is universal familiarity with a molecular diagnostic technique that was largely unknown outside clinical use. The polymerase chain reaction — or PCR — test is the gold standard for detecting infection for the SARS-CoV-2 virus, and billions of such tests have been conducted worldwide. Now, due to this improved awareness of accurate PCR testing during the COVID-19 pandemic, it is increasingly being adopted in non-COVID PCR tests for various kinds of infections such as gastrointestinal infections, respiratory infections, and sexually transmitted infections.

The technique has a 40-year history, and was developed in 1983 by the biochemist, Kary Mullis, who won the 1993 Nobel Prize in Chemistry for the discovery. PCR effectively amplifies selected snippets of DNA, producing millions or billions of copies to the point that they become readily detectable.

In addition to detecting pathogens, it can be used to identify any biological substance containing genetic material, making it useful for diverse fields, including microbiology, forensic science, archaeology and agriculture. It offers many advantages, including being highly accurate, rapid and inexpensive.

New PCR technologies

Seegene, based in Seoul, South Korea, specializes in real-time PCR testing solutions, and has taken this technique to new heights, greatly increasing its usefulness for practical applications. This is in line with the company’s ultimate goal: a world free from diseases, thanks to early diagnosis.

Specifically, Seegene has developed four core technologies that build on each other to advance multiplex PCR assay. The first is the Dual Priming Oligonucleotide (DPO™) technology, which utilizes a unique two-step priming process for target binding. This greatly minimizes the amplification of off-target DNA and enables multiplexing. It also improves specificity and accuracy of the PCR reaction, creating greater confidence in test results.

Tagging Oligonucleotide Cleavage and Extension (TOCE™) technology is a novel real-time PCR chemistry solution to enable detection of multiple targets at specifically designed temperatures with artificial indirect probes. In a single fluorescence channel, Multiple Detection Temperatures (MuDT™) technology separates combined DNA amplification signals of multiple targets into individual ones. Eventually, it provides individual cycle threshold (Ct) values indicating the level of the target material present.

Syndromic testing

The jewel in Seegene’s technological crown is its Multiple Target Ct Detection (3 Ct™) technology, which provides up to 15 quantitative results — three targets per fluorescence channel for five channels — in one tube. Conventional technologies can detect only one analyte per fluorescence channel, offering a maximum of four to five targets per test.

“Our patented PCR technology has the highest multiplicity for quantitative real-time PCR target detection over all other technologies,” notes BooHyun Yang, executive vice president of Seegene’s Patent Center.

Seegene’s technology allows a single PCR test to check for the presence of up to 15 pathogens. This promises to drive down the cost per test due to being able to screen for multiple pathogens at the same time. It also opens the door to syndromic testing, looking for a range of major pathogens that give rise to similar symptoms.

Syndromic testing unlocks endless possibilities. For example, someone presenting with a sore throat and sneezing could be tested for a swathe of respiratory pathogens including SARS-CoV-2, influenza, tuberculosis, respiratory syncytial virus, and rhinovirus. These are traditionally difficult to differentiate because they have very similar clinical symptoms.

Likewise, a person with an upset stomach and diarrhea could be tested for a range of bacteria, viruses and parasites that cause gastrointestinal infections, allowing a doctor to prescribe the appropriate regimen at the first visit instead of taking an empirical approach.

“Our German subsidiary has been providing syndromic assays for gastrointestinal conditions to doctors and labs for several years,” says Seong-Youl Kim, senior vice president of Seegene’s Global Marketing Center. “And they realized that syndromic assay targeting of high-risk pathogens is the best solution for them, so the reimbursement of PCR tests in Germany was changed to include syndromic PCR testing in 2022.”

In another example, up to 14 high-risk human papillomaviruses can be detected at one time, enabling monitoring and screening of cervical cancer that goes far beyond what is possible with pap smear tests. The excellent sensitivity and specificity of this test was confirmed by international clinical studies and publications of key opinion leaders.

One system

Another key aspect of Seegene’s technology is its approach to instrumentation — all tests can be conducted on a single system, the AIOS™ (All-In-One System). Traditionally, molecular diagnostic laboratories have required many instruments from different manufacturers to perform tests for a wide range of pathogens, increasing expense and space demands. This is because certain tests can be only conducted on a specific system, and test kits are incompatible even with different instruments made by the same manufacturer.

But Seegene has adopted a modular system that allows all the tests to be conducted on any of its own instruments. These vary in terms of size and throughput, sharing the same modules or core components. Assays can be applied to all automated systems to be used in large, medium, and small laboratories.

The third component in Seegene’s strategy is the creation of an ecosystem that allows research partners around the world to develop and share their own assays, much as the App store does for new types of application on iPhones.

Realizing that the development of numerous new assays is too big a task for any one company to undertake, Seegene has visionary plans to make their technology and automated development system available globally by partnering with companies and researchers around the world.

Seegene’s Digitalized Development System (SGDDS), a suite of automated development tools, is a key component in these plans. SGDDS is comprised of SG In-Silico, which automates syndromic PCR assay design, and SG IDEA, which automates the testing and documentation during the entire development process. Seegene will make these tools available to prospective global research partners through the company's Open Innovation Program. This will empower researchers from around the world to develop their own assays.

By harnessing resources and talents in this way, Seegene hopes to realize the development of hundreds of assays a year — a massive improvement over the mere handful of assays that other molecular diagnostic companies currently bring to the market.

The COVID-19 pandemic brought the power of PCR diagnostic capacities to the world’s attention, but Seegene is convinced that the full potential of PCR as a technology has yet to be realized.

It plans to unleash this potential through the three key strategies outlined here — syndromic testing based on being able to test for up to 15 pathogens with quantitative information in one test; a modular system that allows assays to be performed with different throughput; and a democratization of assay development and production by making the technology available to global research and company partners.

It is hoped that these new technologies and innovation ecosystem will bring the world closer to Seegene’s vision of a world free from all diseases, thanks to early diagnosis with new assays.

“Seegene’s technologies will provide new insights on PCR-based tests beyond the development of diagnostic products, accelerating the development of new technologies in molecular diagnostics,” says Jik-Young Park, vice president of Seegene’s Research & Development Department. “It will better position society to address emerging threats such as the rise of new pathogens due to ecological changes induced by global warming, thereby preventing future pandemics and realizing healthier lives.