Mirxes Corporation USA, a fully-owned subsidiary of Mirxes Pte Ltd, an RNA technology startup headquartered in Singapore, has revealed that their pioneering product, GASTROClearTM, an in vitro diagnostic test utilizing PCR-based technology, designed for the early recognition of gastric (stomach) cancer, has been accorded the distinguished Breakthrough Device Designation by the US Food and Drug Administration (FDA).

Mirxes Employees FDA Breakthrough designation for Gastroclear

Presentation on Gastroclear

This development signifies a global milestone as it’s the first instance where three significant achievements have converged: 1) an innovative blood miRNA test, 2) an in vitro diagnostic (IVD) tool aimed at the early detection of gastric cancer, and 3) a molecular in vitro diagnostic assay originating from Southeast Asia, all of which have been awarded the esteemed Breakthrough Device Designation by the US FDA. This recognition is exclusively bestowed upon select medical devices that address unmet necessities and deliver heightened efficacy in treating or diagnosing life-threatening or irreversibly debilitating illnesses like cancer.

Unveiled back in 2019, GASTROClearTM holds the distinction of being the planet’s maiden molecular blood examination devised to spot early signs of gastric cancer, empowering both medical practitioners and patients to take proactive measures well before the manifestation of symptoms. The journey of GASTROClearTM’s development and production spans seven years, nurtured by the collaboration of scientists and physicians from esteemed institutions such as the Agency for Science, Technology, and Research (A*STAR)’s Bioprocessing Technology Institute (BTI), Diagnostics Development Hub (DxD Hub), the Singapore Gastric Cancer Consortium (SGCC), the National University of Singapore (NUS), the National University Hospital (NUH), Tan Tock Seng Hospital (TTSH), and Mirxes.

The Singapore Health Science Authority (HSA) granted its approval to GASTROClearTM in 2019 after a prospective clinical validation encompassing more than 5,200 patients within Singapore. In a more recent development, Mirxes, in partnership with seven academic clinical institutions in China, undertook an extensive prospective clinical trial involving over 9,000 patients to secure the registration of GASTROClearTM with China’s National Medical Product Administration (NMPA). Post the pandemic, Mirxes is actively facilitating access to GASTROClearTM in key Asia Pacific markets while simultaneously exploring collaborations to facilitate its introduction within the United States.

As of now, GASTROClearTM is accessible in Southeast Asian markets including Singapore, Indonesia, Malaysia, and the Philippines.

How do you measure miRNA expression patterns?

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a critical role in regulating gene expression. They have been shown to be differentially expressed in cancer cells, making them potential biomarkers for cancer diagnosis. In recent years, advances in miRNA assay technology have made it possible to measure miRNA levels with high sensitivity and specificity. In this blog post, we will take a closer look at the different miRNA assay technologies that are currently available and discuss their advantages and limitations. From RT-qPCR to NGS, we’ll explore the most widely used methods for measuring miRNA levels, including their discovery and quantitative capacities, to cost-effectiveness. Stay tuned to learn more about the latest developments in miRNA assay technology and how they can be used for cancer diagnosis and treatment.

Understanding more about miRNA profiling

The discovery of microRNAs (miRNAs) in the early 2000s marked a significant milestone in the field of genetics and molecular biology. MiRNAs are small, non-coding RNA molecules that play a crucial role in regulating gene expression by binding to specific target genes and preventing their translation into protein. The first miRNA, lin-14, was discovered in C. elegans in 1993, but it wasn’t until a decade later that the full extent of miRNA’s biological significance began to be understood when the let-7 family of miRNAs were uncovered in humans.

In the early 2000s, several groups independently developed high-throughput methods for profiling miRNA expression, which allowed researchers to simultaneously measure the levels of many miRNAs in a single sample. These methods, such as microarray and quantitative PCR and NGS, revolutionized the study of miRNA biology and have been widely used to investigate the roles of miRNAs in various biological processes and diseases. Since then, miRNA profiling has become an important tool for understanding the underlying mechanisms of miRNA-mediated gene regulation and for identifying miRNA biomarkers for various diseases, including cancer.

What technologies are used for the detection of miRNA?

There are several technologies that can be used to measure miRNA levels. Some of the most commonly used methods include:

Reverse transcription quantitative polymerase chain reaction (RT-qPCR): This is a widely used method for measuring miRNA levels. It involves reverse transcribing the miRNA into cDNA, and then using quantitative PCR to measure the amount of cDNA present. This method is highly sensitive and specific, and can be used to measure the levels of individual miRNAs or a panel of miRNAs.

Microarray: Microarrays are devices that can be used to measure the levels of thousands of miRNAs simultaneously. They work by hybridizing labeled miRNA samples to a set of probes on the array, and then measuring the fluorescent signal from the probes. This method is useful for global miRNA profiling, but it is less sensitive than RT-qPCR.

Next-generation sequencing (NGS): NGS is a powerful method for discovering and measuring miRNA levels. It involves sequencing the miRNA samples, and then counting the number of reads for each miRNA. This method is useful for global miRNA profiling and can detect miRNAs that are not known. NGS platforms such as Illumina, PacBio, and Nanopore are the most commonly used.

Digital PCR (dPCR): dPCR is a method that allows for the absolute quantification of miRNA using PCR. It is a highly sensitive method that can detect low levels of miRNA and is useful for rare miRNA detection.

These are some of the most widely used methods for measuring miRNA levels, but new technologies are constantly being developed to improve miRNA detection and quantification.

What is the difference between qPCR and NGS?

Quantitative PCR (qPCR) and next-generation sequencing (NGS) are two widely used techniques for measuring gene expression. Both methods can be used to measure the levels of RNA, including miRNA, in a biological sample, but they have some important differences.

qPCR is a highly sensitive and specific method that can accurately measure the levels of a specific RNA molecule in a sample. It is a real-time PCR method that uses fluorescent probes to detect and quantify the amount of target RNA. qPCR is commonly used to measure the expression levels of small numbers of genes, often a few to several dozens, and it is relatively fast, easy to perform and can be done in a single run. Additionally, using qPCR comes with the acknowledgment that the research knows up front what miRNA targets they are looking to assess.

NGS, on the other hand, is a high-throughput method that can simultaneously measure the levels of thousands or even millions of RNA molecules in a single sample. It is based on the sequencing of millions of short fragments of RNA molecules, followed by computational analysis of the resulting sequencing reads. NGS is a powerful tool for genome-wide expression analysis and can be used to study transcriptomes, epigenomes, and other functional genomic features of an organism. It also allows for the identification of novel and alternative transcripts, splice variants and rare transcripts. However, NGS is a more complex and costly method than qPCR and requires bioinformatic expertise for data analysis.

In summary, qPCR and NGS are both powerful methods for measuring gene expression, but they have different strengths and limitations. qPCR is a highly sensitive and specific method that is best suited for measuring the expression levels of small numbers of genes, while NGS is a high-throughput method that is best suited for genome-wide expression analysis.

Top questions about miRNA expression

What technologies exist for measuring miRNA expression?

MicroRNAs (miRNAs) can be measured using various methods including qPCR, NGS, microarray, and digital PCR.

What is the best way to measure miRNA expression?

There is not necessarily a “best” way to measuring miRNA expression. The best mode of measuring miRNA expression from a “most-quantitative” approach is likely qPCR, whereas from a standpoint of miRNA discovery, NGS is likely superior. Therefore, it depends on the question that a scientist or researcher is interested in answering. A likely perspective is that one may start by first using NGS to sequence there samples of interest and then move on to a more quantitative method like qPCR to make a more valuable assessment of expression profiled of miRNAs.

What is useful about measuring miRNA expression patterns?

Measuring miRNA expression patterns can be useful in several ways. First, miRNAs are involved in regulating gene expression and play a role in various biological processes such as cell growth, differentiation, and apoptosis. By measuring miRNA expression patterns, researchers can gain insight into the underlying mechanisms of these processes and how they may be disrupted in disease states. Additionally, miRNA expression patterns can be used as biomarkers for various diseases, such as cancer, and can help in the development of new diagnostic and therapeutic approaches. Furthermore, studying miRNA expression patterns can also be useful in understanding the basic biology of miRNA and how they regulate gene expression.

Why have you heard of mRNA?

At this point everyone has heard of mRNA. With the advent of the novel vaccines against COVID-19 produced by Pfizer and Moderna, the verbal usage of mRNA has spread outsize of biology classrooms and into the common parlance of everyday life. This is no surprise as mRNA, which stands for messenger RNA, is the key ingredient in producing the new vaccines and charging one’s immune system against COVID-19. But we are not here to get into the nitty-gritty of how the vaccine works. We are here to discuss the fact that there exists another very important type of RNA that you may not know much about.

It is called microRNA (miRNA). As the name implies, miRNA is very small. On the other hand, mRNA is very large. Let’s discuss the key points of each molecule.

What does mRNA do?

mRNA is directly involved in the synthesis of proteins and can be thousands of nucleotides in length. It is made from an enzyme reading a cell’s DNA and then transcribing it into a chain of new building blocks called mRNA. This mRNA is the message that is sent to biological machines in the cell called ribosomes, that read the message of the mRNA and translate it into a protein. Therefore, mRNA uses the coding portion of a gene to produce a protein product.

How are miRNAs different from mRNA?

When comparing mRNA to miRNA there are many differences. miRNAs are significantly shorter at 18-22 nucleotides in length and also are of completely different biological significance. miRNAs are a type of non-coding RNA, because they do not contain information from the cell’s DNA that codes for and consequently produces protein. These tiny non-coding RNA molecules function to regulate the way certain genes are expressed. This interplay occurs through multiple ways: the miRNA can bind to specific mRNA and block them from being read and turned into protein through physical sitting on the mRNA; the miRNA can bind to mRNA and subsequently send the mRNA to be degraded and therefore not turned into a protein.

As you can see miRNA functions as a negative regulator of gene expression through its ability to base-pair in a complementary fashion to target mRNA. Of note, one single miRNA can have many mRNA targets, and one single mRNA may be targeted my many miRNAs. Therefore, there is an incredible amount of gene expression control from many levels of miRNA-mRNA dynamics.

Can miRNA be used to detect cancer?

Circulating biomarkers are a tremendously important topic in modern medicine. Such biomarkers can be used in various ways to detect and monitor diseases, such as cancer. The ability to detect cancer early is vital to extending the lives of patients, because when cancer is found in its early stages the success of treatment is greatly improved. One such biomarker that can be used for detecting cancer is microRNA (miRNA), a string of nucleic acids that is secreted by cells into the bloodstream. Once in the blood, these miRNAs can be measured in various ways that allow doctors and researchers to identify if cancer is present in a patient. Many miRNAs are associated with cancer, and using miRNA for detecting cancer can lead to major breakthroughs in early diagnosis of cancer and greatly extend the lifespan of patients.

Introduction to miRNA and its role in cancer

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a critical role in regulating gene expression. They have been shown to be differentially expressed in cancer cells, making them potential biomarkers for cancer diagnosis. In this blog post, we will discuss how miRNAs can be used to detect cancer in patients.

miRNAs are transcribed from DNA and then processed by enzymes to produce mature miRNAs. These mature miRNAs then bind to specific target mRNAs, leading to either repression or degradation of protein synthesis. miRNAs are involved in many physiological processes such as cell differentiation, growth, and development. They also have a major role in human diseases, including cancer, where they can act as oncogenes or tumor suppressors. Dysregulation of miRNA expression is linked to the development and progression of various types of cancer. Due to their important role in human biology, miRNAs are becoming a promising target for diagnosis and therapy of different human diseases.

miRNA as a biomarker for cancer diagnosis

One way miRNAs can be used to detect cancer is by measuring the levels of specific miRNAs in a patient’s blood or tissue samples. Elevated levels of certain miRNAs have been found in various types of cancer, including breast, lung, gastric, and colon cancer. For example, the miR-125b has been found to be elevated in breast cancer patients and the miR-21 found in lung cancer, whereas certain tumor suppressor miRNAs can be under-expressed in cancer cells, such as miR-16-5p. Measuring these miRNAs levels in the blood of a patient can help in early detection of the cancer. Additionally, miRNA profiling, which is the measurement of multiple miRNAs in a patient’s samples, can be used to classify the type of cancer a patient has.

Whether a doctor or researcher uses one, or multiple miRNAs as a cancer signature depends on the underlying biology of the disease. Once a signature is identified, however, it can be used in detecting the cancer early, allowing early diagnosis, early treatment, and far better patient outcomes. It is a hallmark of cancer research that early detection is directly associated with better survival outcomes.

miRNAs are a useful biomarker for many reasons. First, they are actively secreted into the bloodstream so they are easily accessible to measure through simple blood tests. Second, they are very stable molecules that are less likely to degrade than other biomarkers such as proteins or mRNA. Third, they are far more abundant in blood than commonly used DNA biomarkers, so a smaller sample volume is needed for a meaningful result. Fourth, because there are so many biologically relevant miRNAs related to diseases, they offer a wide berth of options in designing useful cancer signatures for detection and monitoring.

miRNA-based diagnostic tests for cancer detection

miRNAs can be used to detect cancer by using miRNA-based detection and diagnostic tests. These tests can detect the presence of specific miRNAs in a patient’s samples, and can be used to diagnose cancer at an early stage, when treatment is most effective. For example, a test based on the detection of 12 miRNAs has been developed by MiRXES to aid in the detection of gastric cancer. Additionally, the detection of miR-155 in the blood of a patient has been shown as a promising marker for the early detection of lung cancer.

These biomarkers are a promising advancement in cancer detection and will likely bring many useful tests to the healthcare market in the coming years. Another facet of such tests include the fact that they can likely be used in combination with other biomarkers and detection assays to improve their sensitivity and specificity.

In conclusion, miRNAs play a critical role in cancer and have been shown to be potential biomarkers for cancer detection and diagnosis. Measuring the levels of specific miRNAs in a patient’s blood or tissue samples, and using miRNA-based diagnostic tests can help in the early detection of cancer, which is crucial for the success of treatment. Research on miRNA-based diagnostic tests is ongoing and we expect to see more tests being developed in the near future to help improve cancer detection and treatment.