Shanghai Fullgene Biotech Pioneers Aptamer-Based Tuberculosis Diagnostic Platform Ahead of IPO

Tuberculosis is one of the deadliest respiratory infectious diseases, having claimed hundreds of millions of lives over the past two centuries. The World Health Organization’s Global Tuberculosis Report 2020 indicates that in 2019, nearly 2 billion people worldwide had latent tuberculosis infection, and there were approximately 9.96 million new cases of active tuberculosis. In China, the population with latent tuberculosis infection is estimated at around 300 million, with 833,000 new cases, ranking third globally.

High-efficiency, high-precision tuberculosis diagnosis is key to achieving the WHO’s End TB Strategy goals. For a long time, although numerous clinical methods for tuberculosis detection have been available, they have suffered from many drawbacks, including suboptimal specificity and sensitivity, prolonged turnaround times, and high costs. The lack of an accurate, rapid, and cost-effective diagnostic technology has hindered the effective control and prevention of tuberculosis.

Encouragingly, VCBeat has noted that a young startup, Shanghai Fuqing Biology (FULLGE BIOEGHNDLOGY), has successfully developed an aptamer-based fluorescent staining technique for tuberculosis. Integrated with its independently developed FullScan fluorescent microscopy scanning analyzer, this technology can directly differentiate between Mycobacterium tuberculosis (TB) and nontuberculous mycobacteria (NTM) in sputum smears, significantly enhancing the specificity and sensitivity of traditional microscopy. Preliminary studies indicate that its sensitivity is 3–5 times higher than that of conventional acid-fast staining, thereby facilitating the strategic goal outlined in China’s 13th Five-Year Plan for Tuberculosis Prevention and Control: achieving a pathogen-positive rate of over 50% among pulmonary tuberculosis patients.

To further understand the innovation and clinical value of tuberculosis aptamer technology, VCBeat recently conducted an exclusive interview with Zou Guoyuan, co-founder of Shanghai Fuqing Biology.

VCBeat:Why Did the Founding Team Decide to Establish Fuqing Bio? What Opportunities Did They Identify in China’s Niche Segment of Molecular Diagnostics?

Zou Guoyuan:We are deeply grateful to VCBeat. Initially, we hesitated about whether to accept the interview, given that Fullge is a small startup without any notable achievements. However, we later reflected that “though the moss flower is as tiny as a grain of rice, its desire to bloom is no different from that of the peony.” Scattered like stars, these small efforts add a touch of vitality to street corners and alleyways, which is quite meaningful in itself.

Our founding team members initially worked at Daan Gene before venturing into the trading business. Over time, we developed certain insights into the molecular diagnostics industry and began contemplating whether we could create a high-quality product. It was akin to watching people play chess on the street and feeling an irresistible urge to offer unsolicited advice, even though the ancient adage clearly states, “A true gentleman remains silent while observing a chess game.” Let alone making physical moves or interfering directly? Thus, we decided to dive in personally. The greatest advantage of our grassroots background is our heightened sensitivity to the scent of the earth. In other words, we are willing to get down on the ground and peer into every nook and cranny to uncover the truth. Our current tuberculosis aptamer project serves as a prime example that can help you appreciate our approach and mindset.

VCBeat: I am indeed curious. With more than a dozen tuberculosis testing methods already available on the market, why is FULLGE BIOEGHNDLOGY still developing tuberculosis testing products?

Zou Guoyuan:The very fact that numerous tuberculosis detection technologies coexist precisely indicates that no single technology has truly solved the problem. In the face of Mycobacterium tuberculosis, an ancient and cunning “enemy,” if a single decisive strike could seal its fate, why would there be a need to unleash a barrage of arrows?

The question is, where is this sword?

In fact, the precise diagnosis of tuberculosis is a global challenge, far more difficult than testing for the novel coronavirus. Over the course of more than a year, various testing technologies for the novel coronavirus, including nucleic acid, antibody, and antigen tests, have been successively developed, with some now even available for home use. However, since Robert Koch’s discovery of Mycobacterium tuberculosis in Germany over a century ago, there has still been a lack of a precise and convenient diagnostic technology for tuberculosis.

Let us examine a common scenario. The diagnosis of tuberculosis requires a series of cumbersome tests, including imaging, sputum examination, and blood draws. At a hospital in southern China, eight different tuberculosis testing modalities were conducted simultaneously, covering etiology, immunology, pathology, and other disciplines. Faced with a stack of reports—some negative, some positive, some indeterminate, and others showing inconsistent results over time—physicians found it difficult to make clinical decisions, which significantly hindered the precise diagnosis and treatment of tuberculosis. As is well known, tuberculosis is often associated with poverty; the cumulative cost of these numerous tests is prohibitively high.Many patients forgo diagnosis and treatment due to cost considerations, increasing the risk of tuberculosis transmission and making TB prevention and control more challenging.

Tuberculosis prevention and control has become an urgent priority. In response, the Chinese government has attached great importance to this issue and successively issued a series of policies, regulations, and technical standards, including the Action Plan for Containing Tuberculosis (2019–2022), the Technical Specifications for Tuberculosis Prevention and Control in China (2020 Edition), and the Guidelines for Tuberculosis Prevention and Control in Schools in China (2020 Edition).

As an enterprise, how should one meet the substantial demand for tuberculosis (TB) prevention and control? As mentioned earlier, “a single decisive strike,” FULLGE BIOEGHNDLOGY aims to forge such a sharp sword in the field of TB diagnostics—precise and rapid.

Undoubtedly,Like COVID-19, the key to tuberculosis prevention and control lies in the early detection of TB-positive patients.Failure to promptly and accurately diagnose suspected tuberculosis patients inevitably leads to patient attrition, leaving them outside the prevention and control system and becoming ambulatory sources of infection. This recurring cycle consumes substantial medical and economic resources, significantly undermines prevention and control achievements, and exacerbates the severity of the epidemiological situation.

Everyone understands this principle, but how can it be practically implemented? Generation after generation of scientists have continuously tackled this challenge. Through discussions with numerous experts at tuberculosis laboratories, we gained insights into the historical evolution of TB diagnostic methods. While these approaches have addressed the problem to varying degrees and from different perspectives, they still exhibit certain inherent and difficult-to-overcome limitations.

Taking etiological testing as an example, there are currently three methods: sputum smear, sputum culture, and molecular diagnosis.Smear tests are low-cost,However, it cannot differentiate between Mycobacterium tuberculosis and nontuberculous mycobacteria.Tuberculosis and non-tuberculous mycobacteria are very similar, but the clinical medications are completely different, so it is necessary to accurately distinguish between the two;Culture is the gold standard, but the culture period is long, requiring at least two weeks.；Molecular diagnostics, such as PCR, struggle to distinguish between dead and live bacteria.Although the bacteria have been eradicated, the nucleic acids released from lysed bacterial cells require time to be completely cleared from the body. In such cases, even after clinical recovery, nucleic acid test results may remain positive.

In other words, to address the challenge of tuberculosis detection, we must return to the logical starting point of the issue—“Capturing Live Tuberculosis Bacteria in the Shortest Time”。

FULLGE BIOEGHNDLOGY, in collaboration with Shanghai Pulmonary Hospital, has made significant breakthroughs in tuberculosis aptamer research after several years of effort, finally bringing this goal within reach.The first diagnostic reagent based on an aptamer platform in China will be launched in the third quarter of this year,Globally, it is the second such product; the first was the adaptive COVID-19 testing kit launched in the UK in March this year.

VCBeat: The term “aptamer” sounds quite unfamiliar. Could you give us a brief introduction?

Zou Guoyuan:We are all familiar with DNA and its iconic double-helix structure. Aptamers (derived from the Latin word “aptus,” meaning “to fit”) are, in essence, single-stranded DNA molecules comprising dozens of nucleotide bases. Although separated from their complementary strand, these single strands do not remain inactive; instead, they fold into diverse three-dimensional conformations that bind tightly to specific target molecules. This results in exceptionally high affinity and specificity, significantly surpassing those of antigen-antibody interactions. The underlying principle is straightforward: the molecular weight of nucleic acid aptamers is approximately twenty times smaller than that of proteins such as IgE, enabling them to discern subtler structural differences. Much like a 20-megapixel camera captures images with greater clarity than a 2-megapixel one, aptamers offer superior resolution in molecular recognition.

“The name ‘aptamer’ is an excellent translation. For every target, there must be a most suitable and perfectly matched aptamer, akin to a ‘match made in heaven.’ Since it is a ‘heavenly match,’ finding it among countless possibilities requires adherence to the ‘laws of nature.’ Heaven rewards diligence; success cannot be achieved overnight. It took us several years to identify the aptamer for Mycobacterium tuberculosis, which binds immediately upon encountering the bacterium. By labeling the aptamer with a fluorophore, Mycobacterium tuberculosis emitting bright green fluorescence can be easily visualized using fluorescence microscopy. Meanwhile, we have also developed an automated fluorescence microscopic scanning and analysis system capable of replacing manual interpretation.”

From the perspective of technical indicators,The tuberculosis aptamer technology developed by Fuqing Biology can directly distinguish Mycobacterium tuberculosis from non-tuberculous mycobacteria, with a minimum detection limit of 1,000 bacteria/ml in sputum, which is an order of magnitude higher than the traditional acid-fast staining method that requires 10,000 bacteria.As we all know, in the college entrance examination, “one point higher eliminates a thousand competitors.” A tenfold improvement can identify numerous patients who were originally false negatives on smear tests.

Furthermore, the most intriguing aspect of aptamers is“Three-in-One”——It almost integrates the characteristics of the three methods for etiologic detection of Mycobacterium tuberculosis. It is nucleic acid, withMolecular Biologycharacteristics, yet without the need for amplification; it usesImmunologySimilar to the antigen-antibody interaction, yet not an indirect indicator; it can directly presentMorphologyresults.

In the future, we hope that aptamer technology will replace the acid-fast staining of sputum smears, a method that has been used for over a century. Such an advancement would be the best tribute to our predecessors. Some experts, after learning about this technology, stated, “The potential of tuberculosis aptamer technology extends beyond merely replacing smear microscopy; it may even redefine tuberculosis testing.” FULLGE BIOEGHNDLOGY is about to launch a multicenter study to accumulate more evidence-based medical data. Perhaps there will come a day when suspected tuberculosis patients need only undergo an aptamer test to simultaneously resolve multiple challenges previously encountered in tuberculosis diagnosis. Once conditions are mature, we can also leverage the aptamer technology platform to detect a broader range of pathogens.

VCBeat: In addition to the tuberculosis aptamer project, why has FULLGE BIOEGHNDLOGY also entered the molecular POCT field? What is the progress of the company’s molecular POCT product line?

Zou Guoyuan:FULLGE BIOEGHNDLOGY’s short-term goal is to structure its product portfolio around tuberculosis (TB) testing. In addition to the AdaptiDx project, which addresses TB diagnosis, we have also deployed molecular point-of-care testing (POCT) solutions for detecting drug-resistant TB.

Molecular POCT has recently become extremely popular. It seems that any IVD company would feel embarrassed to greet others if it didn’t claim to be developing molecular POCT solutions. However, we have noticed a paradoxical situation: although many companies are entering this field—“wherever there is well water, Liu Yong’s lyrics can be heard”—truly outstanding molecular POCT products on the market remain scarce.

Frankly speaking, the development of molecular POCT is quite challenging.It is by no means easy to achieve a comprehensive balance among “speed,” “outcomes,” and “cost.”, which can even be described as an “impossible trinity”For example, Abbott’s ID NOW offers rapid turnaround but at the cost of amplification efficiency, with a limit of detection (LOD) of only 8,000 copies/mL; nonspecific amplification is also a significant issue. Another example is Cepheid’s Xpert platform, originally developed for tuberculosis testing, which delivers excellent speed and results but comes with prohibitively high costs.

FULLGE BIOEGHNDLOGY’s molecular POCT platform—As I mentioned earlier, we are accustomed to taking a grounded, pragmatic approach. For instance, we consider: What is the reimbursement rate for PCR testing? What is the hospital procurement price? And what share should be allocated to our partners? Based on these factors, it is straightforward to estimate the cost ceiling within which the product must be developed. Some may argue that molecular POCT can command higher pricing. However, we believe this is unlikely under the current macroeconomic and policy landscape. The massive financial burden already incurred by the state for routine COVID-19 nucleic acid testing serves as a cautionary precedent. Moreover, as molecular POCT is poised for widespread deployment across grassroots medical institutions nationwide, higher pricing would certainly not align with the government’s fiscal priorities.

Furthermore, the recently released “Expert Consensus on the Standardized Clinical Application of Rapid Nucleic Acid Testing for Novel Coronavirus” states: “An ideal nucleic acid point-of-care testing (POCT) assay should enable direct detection within the same closed, portable, all-in-one instrument immediately after sample collection, featuring simple operation and a significantly shorter turnaround time for the entire testing process compared to conventional SARS-CoV-2 nucleic acid testing.......However, due to limitations in technological development, the aforementioned ideal scenario has not yet been achieved.”

We take the liberty ofFULLGE BIOEGHNDLOGY’s molecular POCT prototype, which “achieves the aforementioned ideal,” will be officially unveiled before China’s National Day in 2021.Detailed information about this product will be shared with everyone at that time.

Interview Notes:

At the conclusion of the interview, VCBeat noted a simple yet heartfelt interpretation of Fullgene’s name. “Fuqing” (Fullgene): “Harmonious and clear, enriching life,” translated into English as “Full gene, Full life.” Much like aptamers, this pairing seems a match made in heaven between the Chinese and English versions.