COVID virus showsn as blue spheres in a microscopic view

This colorized scanning electron microscope image shows SARS-CoV-2 (round blue objects), the virus that causes COVID-19, emerging from the surface of cells cultured in the lab. [Image courtesy of National Institute of Allergy and Infectious Diseases]

New startup Spear Bio plans to commercialize ultrasensitive protein-detection technology from Harvard University’s Wyss Institute for Biologically Inspired Engineering.

Boston-based Spear Bio licensed the DNA nanotechnology-driven Successive Proximity Extension Amplification Reaction (SPEAR) in a worldwide exclusive agreement with Harvard’s Office of Technology Development.

Spear Bio will develop a reagent-based platform for ultrasensitive protein detection in small-volume samples with an initial focus on research-use-only applications, Harvard said in a news release.

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The first efforts will be to commercialize an assay for using a drop of blood or other biofluids to measure neutralizing antibodies (NAbs) against SARS-CoV-2, the virus that causes COVID-19 disease. Measuring those antibodies can help understand protective immunity and vaccine efficacy, and doing so with small samples can enable new research and diagnostics.

“The extreme sensitivity in very small sample volumes provided by SPEAR, and the fact that it can be read out using common quantitative PCR equipment, offer unique potential for creating microsampling-based in vitro diagnostics that can transform academic and clinical research in multiple disease areas,” Spear Bio co-founder and Chief Technical Officer Feng Xuan said in the release.

Xuan developed the technology with co-inventors Cherry Fan and Yu Wang. Wang is now Spear Bio’s acting head of application development. They were all members of Wyss Core Faculty member Peng Yin’s group.

“The invention of SPEAR was enabled by key advances in DNA nanotechnology that we made at the Wyss over the years, including the prescribed and signal-dependent synthesis of readable DNA sequences,” said Yin, who is also a Spear Bio co-founder. “The detection platform that Feng Xuan built and then substantially de-risked with other members in the lab, now has significant potential for developing immunoassay products for clinical research and in vitro diagnostics in the near-term.”

Yin the founder of other startups using Harvard-licensed tech, including 3EO Health, which is commercializing an at-home, PCR-grade COVID testing system.

How the SPEAR technology works, in Harvard’s words:

“In SPEAR … miniscule amounts of proteins, including NAbs, can be detected via target-binding probes that bind to different but proximal sites in a protein’s structure. This proximal double-tagging event allows the two probes to ‘shake hands,’ with their interaction triggering a specifically engineered successive extension reaction, and synthesis of a unique DNA sequence which then can be amplified and quantified using standard qPCR instruments. Importantly, in the absence of detection targets, the interaction between free-floating probes does not allow the synthesis of the complete DNA sequence, significantly reducing the background compared to conventional proximity-based assays. SPEAR is superior to other protein detection assays in its combination of extreme sensitivity, wash-free workflow, and functionality over a large range of target protein levels (dynamic range) with the ability to be fully effective in sample volumes as small as 1 uL. The technology was de-risked with the help of the Wyss’ translation engine, in which it received the status first of a Validation Project, and then of an Institute Project, designated to support the development of high-value technologies with high potential for market success.”