Mantle Biotech finds inspiration in the ingenuity and diversity of extremophile biology.
We leverage tools used in the pharmaceutical industry to produce bespoke binding proteins that are heat-stable, low-cost, and versatile. We screen through massive libraries of candidate proteins to identify unique versions which bind to the target of interest with high affinity and specificity.
Our technology platform sits at the intersection of chemical engineering, protein engineering, cell biology, and medical diagnostics.
The immensity of protein sequence space makes it a statistical impossibility to identify new functional proteins at random. To overcome these odds, we produce a large randomized library of binding candidates, all based on a common, robust scaffold protein originating from thermophilic microbes.
Then, we array those binding candidates on the outside of yeast cells (a technique called “yeast surface display”). Each yeast cell acts as a champion for its own binding candidate (and the DNA which encodes for it), and we can use fluorescent protein labeling and cell sorting techniques to identify those yeast cells carrying rare functional proteins.
Yeast-surface display was pioneered as a protein engineering technique in the late 1990s, and was leveraged to great effect in the pharmaceutical industry. Our founding team is the only research group that has the demonstrated capacity to effectively apply this powerful technique to the diagnostics industry.
- Miller E.A., Sikes, H.D. (2015) Addressing Barriers to the Development and Adoption of Rapid Diagnostic Tests in Global Health. Nanobiomedicine 2(6):1–21. https://doi.org/10.5772/61114
- Miller, E.A., Traxlmayr, M.W., Shen, J., Sikes, H.D., 2016. Activity-based assessment of an engineered hyperthermophilic protein as a capture agent in paper-based diagnostic tests. Mol. Syst. Des. Eng. 1, 377–381. https://doi.org/10.1039/C6ME00032K
- Miller, E.A., Baniya, S., Osorio, D., Al Maalouf, Y.J., Sikes, H.D., 2018. Paper-based diagnostics in the antigen-depletion regime: High-density immobilization of rcSso7d-cellulose-binding domain fusion proteins for efficient target capture. Biosens. Bioelectron. 102, 456–463. https://doi.org/10.1016/j.bios.2017.11.050
- Miller, E.A., Jabbour Al Maalouf, Y., Sikes, H.D., 2018. Design principles for enhancing sensitivity in paper-based diagnostics via large-volume processing. Anal. Chem. 90, 9472–9479. https://doi.org/10.1021/acs.analchem.8b02113
- Sung, K.-J., Miller, E.A., Sikes, H.D., 2018. Engineering hyperthermostable rcSso7d as reporter molecule for in vitro diagnostic tests. Mol. Syst. Des. Eng. 3, 877–882. https://doi.org/10.1039/C8ME00049B
- Zhang, Q., Zeininger, L., Sung, K.-J., Miller, E.A., Yoshinaga, K., Sikes, H.D., Swager, T.M., 2019. Emulsion agglutination assay for the detection of protein–protein interactions: an optical sensor for Zika virus. ACS Sensors 4, 180–184. https://doi.org/10.1021/acssensors.8b01202
- Paloni, J.M., Miller, E.A., Sikes, H.D., Olsen, B.D., 2018. Improved ordering in low molecular weight protein-polymer conjugates through oligomerization of the protein block. Biomacromolecules 19, 3814–3824. https://doi.org/10.1021/acs.biomac.8b00928
- Miller, E.A.*, Sung, K-J.*, Kongsuphol, P., Baniya, S., Aw-Yong, H.Q., Tay, V., Tan, Y., Kabir, F.M., Pang-Yeo, K., Kaspriskie, I.G., Sikes, H.D., 2020. Beyond epitope binning: directed in vitro selection of complementary pairs of binding proteins. ACS Comb. Sci 22, 49–60. https://doi.org/10.1021/acscombsci.9b00176