The TRAC was established in 2010 at the Donnelly Centre at the University of Toronto. The TRAC follows the Donnelly Centre philosophy, which is centered around multidisciplinary research with an emphasis on the development and application of functional genomics technologies. The development and implementation of the TRAC is a concerted effort led by Drs. Sachdev Sidhu and Jason Moffat and involves collaborations with many talented researchers from the Donnelly Centre and other research centres.
The TRAC has assembled a world-class team made up of some of Ontario's most prominent scientists and clinician-scientists with an unusually broad repertoire of research expertise and biological interests, tools, and reagents. The combination of this expertise with TRAC's powerful technologies allows the Centre to produce thousands of high-quality antibodies and biologics against numerous diverse targets, which can be immediately evaluated for therapeutic and research potential.
While the TRAC initially focused on the generation of synthetic proteins using antibody scaffolds, it has now expanded the realm of small proteins that can be engineered to produce modulators of protein function. Notably, libraries of protein variants built on the ubiquitin scaffold have been successfully used to produce inhibitors and activators of enzymes in the ubiquitin proteasome system. Other scaffolds are currently being engineered into libraries of variants that can be screened for binding to a wide variety of targets.
The TRAC is staffed by a talented scientific team of research associates, post-doctoral fellows and technicians working under the supervision of Drs. Sidhu and Moffat on various collaborative projects with academic and industrial partners.
Recognizing the need for a focused mechanism to take TRAC discoveries to the next step towards translation into commercializable products with benefits to patients, Dr. Sidhu established the Centre for the Commercialization of Antibodies and Biologics (CCAB) in 2014. The CCAB interacts with TRAC scientists to provide support and expertise in product development, industrial production, IP protection and venture capital fundraising.
- To generate a broad repertoire of high quality, high affinity synthetic proteins using state-of-the-art phage display technology in a high-throughput pipeline.
- To evaluate the potential of synthetic proteins as biological reagents, diagnostic and prognostic tools, and therapeutic candidates, in partnership with a world-class team of experts.
- To share antibody and biologics reagents with research experts around the world to advance knowledge of biological processes and discovery of new therapies for a wide variety of diseases.
Since its inception, the TRAC has generated thousands of therapeutic-grade antibodies against hundreds of distinct human antigens. Selections against well-folded antigens have a >90% success rate. The TRAC has also established a rapid affinity maturation strategy that can be applied to pools of binders to generate antibodies with subnanomolar affinities, which are as good or better than conventional hybridoma antibodies. Additionally, the TRAC has optimized a new, proprietary method (CellectSeq) to screen phage-displayed libraries of antibodies directly against targets expressed on cells, bypassing the need for antigen purification. This is especially relevant to membrane-associated proteins, which represent more than 70% of drug targets. The TRAC has also built and optimized several phage-displayed libraries of synthetic antibodies in various formats (e.g. antibody fragments (Fabs), single chain variable fragments (scFvs)), and is currently developing an array of novel antibody formats (e.g. autonomous VH domains, diabodies, bi-specifics, BiTEs) for various applications. Antibodies produced by the TRAC have been used to detect secreted and cell surface proteins in cell biology experiments, and have been validated as effective probes and modulators of cell signaling. Some of the antibodies produced at TRAC are currently being further developed as therapeutics by industrial partners such as Northern Biologics and Celgene.
In collaboration with Sidhu and Moffat lab researchers, the TRAC’s high throughput phage display-based pipeline has been used to generate variants of ubiquitin targeting more than 100 proteins in the ubiquitin proteasome system thus far, with the goal of eventually targeting all ubiquitin-binding proteins. These variants have been validated as highly specific modulators for the activity of their targets, with potential benefits for new therapeutics development, in collaboration with academic experts in the field. The ubiquitin variants are being further developed for commercial and therapeutic purposes in collaboration with industrial partners such as Boehringer Ingelheim.