I-Corps: Self-assembling, protein-based contrast agent targeted to collagen Type 1

New York University, New York NY

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is the development of a preclinical imaging agent for non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common chronic liver disease worldwide, with some estimates placing its prevalence at 25-30% of the adult population in developed Western nations. Because NAFLD develops insidiously, it may be difficult to detect in its early stage, and diagnosis is often incidental. A hallmark of the disease is inflammation and progressive fibrotic collagen deposition in the liver, leading to liver failure. Although biopsy is the gold standard for diagnosis, it is invasive and, therefore, not preferable. The proposed noninvasive longitudinal imaging technology fulfils many of these testng needs. In addition, the exploration of self-assembling proteins as biomedical imaging agents may also be used for other targets such as kidney or lung diseases. This I-Corps project is based on the development of a self-assembling, protein-based contrast agent targeted to collagen type I for non-alcoholic fatty liver disease (NAFLD). The technology seek to improve noninvasive diagnosis and monitoring of NAFLD in vivo. The core technology, Type I collagen-binding thermoresponsive assembled protein or COL1-TRAP, is a recombinant protein amphiphile composed of a type I collagen binding peptide fused to a pentameric coiled-coil (C) domain and an intrinsically disordered elastin-like polypeptide (ELP) domain. COL1-TRAP forms hierarchical, multimeric micelles at room temperature. These micelles are distinguished by their reversible self-assembly and disassembly in solution, forming a versatile class of stimuli-responsive materials with diverse applications. Recombinantly expressed protein micelles are of particular interest due to their hierarchical folding and potential for multivalent targeted interactions with binding ligands. The multimeric self-assembled structure means that a relatively short binding sequence with a moderate affinity for collagen may be used, with the combination of weak interactions summing to a high affinity interaction. The result is a targeted, high affinity smart binder for collagen type I. Tracking of collagen type I deposition may help visualize the fibrosis across the liver as NAFLD progresses. In addition, the proposed technology may form the basis for more sensitive and effective noninvasive imaging agents. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.