A proven molecular diagnostic that helps oncologists better manage cancer

It was when Wren founder Dr. Irvin Modlin first asked, “How do we know we’ve excised all of a NET when we operate?” that utilizing molecular information in a blood sample as a window into neuroendocrine tumor activity first occurred to him. 

It was a question he had pondered from his early days as a gastrointestinal surgeon right up to the time he served as Vice Chairman of the Yale University School of Medicine Department of Surgery in New Haven.

It was also at Yale where Modlin met Wren Scientific and Laboratory Director Dr. Mark Kidd. Dr. Kidd had been studying the molecular pathophysiology of gastrointestinal neuroendocrine cells as an NIH-funded research scientist at Yale’s Gastric Surgical Research Group.


Key Moments in the Development of Our Science

It was at Yale University School of Medicine where Dr. Modlin met Dr. Mark Kidd, and where their shared interest in neuroendocrine tumor biology served as a foundation to put them on the path to creating a better way to diagnose residual NET tumor presence after surgery.

In 1996, Modlin and Kidd collaborated on their first peer-reviewed paper discussing neuroendocrine cell secretion behavior, laying the foundation for over 200 papers, presentations, and studies on the application of molecular diagnostics in the detection, characterization, and treatment monitoring of NETs.

Two decades of collaboration between Modlin and Kidd–and a host of other researchers, scientists, and oncologists–yielded the answer to Dr. Modlin’s question, provided a proven methodology to diagnose NETs, and served as the foundation to establish Wren Laboratories in June of 2014.


mRNA as a NET Biomarker 

Biomarkers are indicators produced by tumor cells that can be detected in blood or other bodily fluids and signal the presence of cancer. Commonly used protein biomarkers for neuroendocrine tumors and other cancers are not specific and typically signal other conditions. This is where mRNA as a biomarker comes into play.

We Focus on mRNA

Messenger RNA, or mRNA, are genetic molecules expressed by cells and found in a patient’s bloodstream. Human cells have about 22,000 different mRNAs that help control a wide variety of operations. Cancer cells also produce mRNA molecules and while they are aberrantly expressed, they provide unprecedented information about tumor biology which can be used to characterize a tumor and demonstrate how it is responding to therapy.

More Robust than Medical Imaging

Medical imaging techniques like CTs, MRIs, or PETs offer a static view to determine tumor presence. In contrast, our mRNA-based methodology provides dynamic and precise information about tumor behavior in real-time, aiding in prediction. Blood-based mRNA diagnostics surpass traditional protein biomarkers in accuracy, sensitivity, and specificity, often being 2–10 times more precise.

How it works

mRNA Collection, Isolation, and Amplification

Blood Sample is Collected

After a doctor consult, our process begins with a simple, relatively painless blood draw at a local lab.

Sample Shipped to Wren Laboratories

The sample, mixed with our proprietary buffer solution, is stabilized and protected during transit.

mRNA Isolation

We isolate the mRNA, a process enabled by our buffer, which facilitates the breakdown of the cellular membrane. 


The mRNA is reverse transcribed into cDNA and then amplified using PCR with gene-specific primers. 

The Art of the Algorithm

Analyzing the mRNA sample

After qPCR, the analysis of the processed test sample begins.

We use a proprietary suite of algorithms that have been constructed with anonymized patient data from over the last two decades. We employ Artificial Intelligence to identify potential molecular signatures, cross-referencing them with clinical and scientific data.

Our NETest, for example, measures the expression levels of 51 genes that are specifically associated with neuroendocrine cancer.

Our final gene panels are selected using artificial intelligence, and then assessed by our scientific experts and validated by our lab technicians. 

The NETest Score provides accurate, clear and clinically useful information about the disease state of a neuroendocrine tumor.

We feed our sample information into our MultiAnalyte Algorithm Analysis (MAAA) and use the output to calculate the risk that the gene expression measured in blood is cancerous and how robust that activity is.

We then convert these calculations into a score that can be used clinically to provide actionable information about the disease state of a tumor or other disease.

With the NETest score, for instance, we calculate a percentage ranging from 0 to 100%, where a higher score indicates an increased risk of tumor activity at the time of testing.

What’s Next?

The Future of our Science

The NETest and the NETest PPQ, both widely available and readily obtained from us in conjunction with a doctor or oncologist, represent our current commercial offerings. We are very close to releasing a prostate cancer diagnostic, the PROSTest, which has garnered enthusiasm and interest. In July 2021, our saliva-based COVID-19 test received an FDA EAU and was met with broad personal and organizational utilization.

The combination of mRNA diagnostics based on saliva and blood biopsies reflect the basis of our scientific strategy and pipeline:  the development of a series of gene signatures that identify the disease state of cancer, provide information that can be used for rapid identification of disease and recurrence and help to determine the efficacy of therapy.