TET Tethered Enzyme Technology (TET) comes from the groundbreaking work by Professor Alex Travis and Roy Cohen at Cornell University that replicates the way that enzymes attach to mammalian sperm providing improved stability and activity. Professors Travis and Cohen have evolved these patented techniques to facilitate fast, high sensitivity catalytic coupled reactions that are first being applied to the detection of biomarkers including proteins, enzymes, viruses and Micro-RNAs.
Initially funded by a prestigious NIH Pioneer Award because of its transformative potential, the underpinnings of our technology have been developed with over $6M in grants and academic support. TET nanobots are capable of performing chemical operations with high sensitivity, specificity, and ultra-rapid speed typically with improved amplification and read-out time faster than when based on antibody-antigen interactions. Tethering of enzymes to nanoparticles also results in extraordinary stability, with NSE-FAST having an early lab-tested freezer shelf life of over one year. Multiple types of nanobots can be combined in test and reaction control wells in our unique 12 well strips, on a standard assay plate or in other assemblies to perform diverse chemical operations such as detection of a wide variety of analytes and biomarkers. TET enables a practically infinite array of possible reactions – a true multi-purpose molecular software platform.
Tethered Enzyme Technology (TET) was inspired by nature. Studies of how sperm generate energy to swim revealed that they attach the enzymes that metabolize sugar to a solid structure down the length of the sperm tail. This solid-state design lets them carry out complex reactions in a small space and with high efficiency—producing energy exactly where it is needed. We recognized that if we could copy their design on man-made surfaces such as nanoparticles, then we could create ultra-fast molecular machines, that could perform an almost endless variety of functions. This concept of attaching enzymes to structures to add function has been around for decades, but the most common methods of attachment usually result in the enzymes having low activity. However, by copying the design of sperm, we were the first to show coupled reactions from a biological pathway tethered to a single surface (REF to Mukai paper). We showed the enormous advantage of TET versus traditional tethering methods (REF to Gao paper), and we were able to show that TET reactions showed even greater activity than those same enzymes in solution (REF to 2015 paper). The advantages of TET have enabled us to exponentially increase the complexity of tethered enzymatic reactions, demonstrating a 10-step tethered reaction, metabolizing glucose to lactate, as done in the sperm tail (REF Mukai Angewandte paper).
Because of the enormous potential for medical diagnostics and therapeutics, our work has received much attention, from our first abstract being chosen for a press release by the American Society for Cell Biology (approximately one of 20 out of 10,000), to significant press coverage of our Pioneer Award from the National Institutes of Health. On the strength of our pre-clinical data distinguishing patients with brain injury from those with mimics, our solid intellectual property with multiple issued patents and more at various stages of prosecution, and those enormous potential impacts, TETmedical was founded in December 2021. At this time, TETmedical is transitioning from work in the Cornell laboratories of Drs. Cohen and Travis to its new home in the Cornell Center for Life Science Ventures incubator.
Product Development Strategy and Pipeline
Recognizing that what most separates TET from antibody-based approaches is our incredible sensitivity and speed, we are focusing our first products on medical conditions where rapid, quantitative measurements of biomarkers or analytes are urgently needed, and current diagnostics do not exist. Brain injuries such as stroke presented an obvious first target. Tests for other conditions for which there are no objective diagnostics are also being developed by TETmedical.
The COVID-19 pandemic presented new medical challenges to the world, including the need to quickly distinguish viral infections such as influenza, COVID-19, respiratory syncytial virus, and adenovirus. We have stepped up to meet this need, inventing new TET-based modalities for differential diagnosis of these conditions, and are developing a new line of diagnostic products for diagnosis of viral infections. This work is currently supported by the New York State Biodefense Commercialization Fund.
Simultaneous with these efforts, we have also developed a TET-based modality to detect specific microRNA sequences. Using a similar strategy of identifying a medical need where rapid diagnosis is essential, but no diagnostics currently exist, we chose to develop as a first product in this line, a point-of-care test for canine hemangiosarcoma. Work at Cornell from the laboratory of Dr. Scott Coonrod at the Baker Institute for Animal Health identified several candidate microRNA sequences that could identify canine hemangiosarcoma from similar conditions. We are performing early-stage product development toward this goal, with support from the Riney Canine Health Center.
- Effects of Nanoparticle Size on Multilayer Formation and Kinetics of Tethered Enzymes
- Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate
- Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection
- Improved monitoring dynamics through use of a tethered enzyme biosensor to detect and quantify neuron-specific enolase activity levels in biofluids
- Biomimicry Enhances Sequential Reactions of Tethered Glycolytic Enzymes, TPI and GAPDHS
- The Potential for microRNA Therapeutics and Clinical Research
In August 2022 TETmedical formally licensed from Cornell the 3 issued and 3 pending patents on the diagnostic use of TET. The 3 issued patents apply to the TET assays for acute brain injury associated with the NSE-FAST product. Pending patents apply to other applications including use of TET for detection of viruses and micro-RNAs. The list of issued and published patents is below. The pending applications have the potential to allow customizable detection of single strand RNA from a virus or micro-RNA with specificity to a single base pair directly in minutes without the need for PCR or sequencing.
TETMedical Filed Patents
In December 2022 TETmedical filed its first patent as a provisional patent covering the innovative design of the NSE-FAST including the design of the 12 well TET strip, production of the enzymes used, the tethering process, the process for layering the components into test, positive and negative control wells and concepts for at home and point of care use of TET for diagnostic applications. New patents are being developed for design of the products that use TET for virus and micro-RNA diagnostic applications.
Grant Funding Status
In addition to equity funding of the company, TETmedical/Cornell is currently funded from 3 grants totaling $1.25M with applications in for another $1.4M of grants.