Wyss startup Spear Bio launched to empower disease research, disease diagnostics, and patient care with the Institute’s ultrasensitive, DNA nanotechnology-driven protein-detection technology called SPEAR.
The Problem
Being able to accurately measure the levels of proteins, such as, for example, antibodies produced by the body against invading pathogens (immunity) or its own proteins (autoimmunity), hormones, and biomarkers reporting the presence or progress of diseases, is key to understanding and diagnosing pathological processes in patients, and developing new drugs and vaccines. However, usually such measurements require work-intensive procedures that have to be performed on specialized laboratory instruments, and need larger sample volumes to be processed and stored appropriately.
Our Solution
To overcome these challenges, Wyss Institute Core Faculty member Peng Yin, Ph.D. and his former Postdoctoral Fellow Feng Xuan, Ph.D. developed the SPEAR technology. SPEAR, which stands for “Successive Proximity Extension Amplification Reaction,” enables the detection of miniscule amounts of proteins via target-binding probes that bind to different but proximal sites in a protein of interest’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. This significantly reduced 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. Propelled by diagnostic gaps in the COVID-19 pandemic, the team developed their first assay to measure SARS-CoV-2-directed NAbs in a drop of blood from a finger-stick and in dried blood spot samples.
The generation and levels of NAbs are a key metric for understanding protective immunity and vaccine efficacy, and SARS-CoV-2 NAb-detecting assays are tools used by the Centers for Disease Control, as well as vaccine and drug developers, to determine the susceptibility of individuals to COVID-19. The ability to sensitively and accurately quantify them in small, easy-to-obtain patient samples could significantly increase the depth and throughput of such studies, 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. 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.
Product Journey
Xuan, co-inventors Cherry (Tsz Wing) Fan, Ph.D. and Yu Wang, Ph.D., and other members of the group de-risked the SPEAR technology with the help of the Wyss’ translation engine, in which the project received the status first of a Validation Project, and then of an Institute Project. The latter is reserved for significantly validated high-value technologies with outsized potential for market success.
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.
In 2022, the SPEAR technology was permanently licensed to Spear Bio Inc., a Boston-based startup envisioned at the Wyss Institute and co-founded by Yin and Xuan. Earlier, the company had already been granted access to SPEAR on a non-exclusive basis for a limited term, in accordance with the University’s commitment to the COVID-19 Technology Access Framework. In the spirit of the Wyss-specific Institute-startup continuity, Xuan became Spear Bio’s CTO, and Wang joined the company as Head of Application Development, with both joining the Wyss Lumineers class of 2021.
Impact
Spear Bio’s first order of business will be the commercialization of the ultra-sensitive assay for measuring NAbs against SARS-CoV-2 with the bigger plan to build a more broadly applicable reagent-based platform for ultrasensitive protein detection in small-volume samples.