This SBIR Phase I project will further the development of an orally administered gene delivery vehicle called the Crypt-Reaching Particle (CRP) that is able to overcome the physical barriers of the mucus to deliver DNA-based drugs to the cells of the gastrointestinal tract. The therapeutic agent will then be expressed as a protein locally in the gastrointestinal tract or be secreted into the bloodstream to treat the full body. Development of this vehicle will lead to novel scientific insights on DNA delivery that will benefit and educate the field of fundamental science and engineering. Successful commercialization would benefit pharmaceutical companies by providing an oral drug delivery platform for approved and novel drugs, U.S. patients by reducing the need for injectable drugs and thereby increasing compliance and quality of life, and payers by reducing costs associated with injectable drugs and improving outcomes by increasing patient compliance via oral administration. The drug-agnostic feature provides broad and diverse market opportunities within the rapidly expanding market for biologics, among other therapeutic agents leading to substantial job creation. As an example, a potential addressable market in four areas (i.e., delivering TNF inhibitors, protein replacement, peptide hormones, and blood factors) exceeds $90 billion per year.
This project is designed to prepare a stable oral formulation of the Crypt-Reaching Particle (CRP), a novel drug-agnostic drug delivery vehicle, and demonstrate that it can deliver a functional DNA cargo for expression and secretion in intestinal epithelial cells in vitro and in vivo. This project focuses on the technical challenges associated with preserving the functionality of a DNA cargo as an example of a challenging drug delivery scenario that is difficult to replicate. The innovation is the design of the vehicle to penetrate through the mucus and transfect underlying epithelial cells by mimicking the enteric poliovirus. This will lay the foundation for the first oral gene therapy. Briefly, the project will address three objectives. First, preparation of a formulation for the CRP for oral administration via lyophilization with analyses to assess formulation and DNA stability as a function of time, temperature, and pH. Second, testing the ability of the orally formulated CRP to deliver a functional DNA plasmid encoding Gaussia luciferase to Caco-2 intestinal epithelial cells in vitro by measuring both cellular and secreted expression. Finally, testing the ability of the orally formulated and administered CRP to deliver a functional Gaussia luciferase plasmid to intestinal epithelial cells in vivo in Fischer 344 rats to assess expression and secretion.
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.
