A Boston-based startup, Spear Bio, is being launched by the Wyss Institute at Harvard University to commercialize their DNA nanotechnology-driven ultrasensitive SPEAR (Successive Proximity Extension Amplification Reaction) protein-detection technology. The company will develop a reagent-based platform for ultrasensitive protein detection in small-volume samples with an initial focus on research-use-only applications.
SPEAR technology enables ultrasensitive protein detection in small patient samples, such as a drop of blood from a finger-stick, dried blood spot samples, and other biofluids obtained with the help of micro-sampling techniques, while leveraging existing laboratory equipment, including qPCR machines.
Spear Bio plans to use the SPEAR technology to build a more broadly applicable protein detection platform, and will first focus on commercializing an ultra-sensitive assay that can accurately measure the levels of neutralizing antibodies (NAbs) against SARS-CoV-2.
The ability to sensitively and accurately quantify NAbs in small, easy-to-obtain patient samples could significantly increase the depth and throughput of studies trying to understand protective immunity and vaccine efficacy, and enable various types of future research and diagnostic assays.
“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 Peng Yin, PhD, a lead of the Wyss Institute’s Molecular Robotics Initiative, professor of systems biology at Harvard Medical School, and a co-founder of Spear Bio. “The detection platform that Feng Xuan, PhD, 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.”
In SPEAR, minuscule 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.
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 offers extreme sensitivity, a 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 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,” said Xuan, co-founder and CTO at Spear Bio.
The company plans to use the assay to develop research and diagnostics applications that require the ultrasensitive and quantitative detection of protein biomarkers in small samples. “SPEAR’s unique capabilities give us a clear value proposition for market entry,” said Oliver Tassinari, senior director of business development at Spear Bio. “We are now laser-focused on translating the exceptional technical performance of the assay technology to a satisfying customer experience to solve research and diagnostics-related problems.”