Harvard’s Wyss Institute spins out protein detection technology to create Spear Bio

By Nick Paul Taylor, The Science Advisory Board contributing writer

August 24, 2022 -- The Wyss Institute for Biologically Inspired Engineering at Harvard University has licensed technology for detecting proteins in small patient samples to a newly formed startup.

Using the license, the Spear Bio startup will develop a reagent-based platform for ultrasensitive protein detection in small-volume samples, such as blood from a finger stick and dried blood spot samples, with an initial focus on research applications of the technology.

Specifically, the startup will prioritize the development of an assay for accurately measuring the levels of neutralizing antibodies against SARS-CoV-2. Enabling researchers to quantify antibody levels in small, easy-to-obtain patient samples could boost the depth and throughput of studies designed to determine the susceptibility of individuals to COVID-19.

The Spear technology, an acronym of "Successive Proximity Extension Amplification Reaction," is built on Wyss' advances in nanotechnology such as the prescribed and signal-dependent synthesis of readable DNA sequences. Feng Xuan, a co-founder of Spear Bio who has taken up the role of chief technology officer, worked with the advances to build and de-risk a detection platform.

Using the platform, Spear Bio aims to enable the detection of small amounts of protein via target-binding probes. The probes bind to different but proximal sites in a protein's structure in an interaction that leads to a specifically engineered successive extension reaction and synthesis of a unique DNA sequence. The DNA sequence is then amplified and quantified using quantitative polymerase chain reaction (qPCR) instruments.

"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," Xuan said.

In the absence of detection targets, the interactions between free-floating probes do not trigger the synthesis of the complete DNA sequences, thereby "significantly reducing the background compared to conventional proximity-based assays," according to Wyss. The researchers view the sensitivity, wash-free workflow, and functionality over a large range of target protein levels and effectiveness in sample volumes of 1 uL and up as other advantages of the technology over existing protein detection assays.

While Spear Bio is initially focused on detecting anti-SARS-CoV-2 neutralizing antibodies, it sees a range of research and diagnostic applications for the technology. Any task that requires the ultrasensitive and quantitative detection of protein biomarkers in small samples is theoretically applicable to Spear.

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