Alanna Schepartz, Sterling Professor of Chemistry at Yale, will be the first to admit that she didn’t invent the idea of exploiting positive charge to move proteins into cells. There have been countless studies focused on a positively charged segment of Tat, for instance, a protein made by HIV that helps the virus to quickly replicate. Scientists have long wanted to know: How could this phenomenon be used in medicine? How could we hijack that process to penetrate the cell’s inner fluid or cytosol, and even the nucleus, to change the course of disease?
But the field, says Schepartz, ran into roadblocks. For years, she says, “Scientists believed their molecules were making it into the cytosol, but they weren’t—at least not much—because they were trapped inside cell vesicles known as endosomes.”
Schepartz had been working for more than a decade in her own lab to understand how to take control of the endocytic pathway to move proteins into the cytosol, when she made a serendipitous discovery of a molecule that could travel into endosomes and into the cytosol and nucleus of mammalian cells with unprecedented efficiency. The discovery of cell-penetrating miniature proteins (CPMPs) has become the basis of a platform technology for therapeutic delivery. Schepartz is now in the process of developing the commercial potential of this technology to deliver protein-based therapeutics directly into cells. The technology was chosen as one of four $300,000 Development Grant awardees from the Blavatnik Fund for Innovation at Yale, which is managed by the Office of Cooperative Research (OCR), and took first place ($5,000) in the Biotech Pitch Contest at the OCR-led Yale Innovation Summit on May 10.
This funding, she says, will be critical in advancing her research to the place where she and her team can examine its effectiveness in treating specific disease. “The beauty of the Blavatnik program is it allows us to evaluate the therapeutic uses of the technology—and to assess in vitro or in vivo pharmacological properties in the context of a disease,” Schepartz says.
They’ll start by focusing on Type 1 Citrullinemia, a rare genetic disorder that causes ammonia and other toxic substances to accumulate in the blood resulting in vomiting, seizures and loss of consciousness. There is currently no cure.
“Like many academic technologies that develop commercial prospects, the CPMP platform has evolved through open-minded engagement with people and ideas outside of academia,” says David Lewin, Senior Associate Director of Business Development at OCR. “Success requires imagination, endurance, and the will to engage those who view scientific findings through non-academic lenses. Alanna has been a model of engagement and responsiveness to these views.”
Advisors working with Schepartz during the Blavatnik application process encouraged her to focus on a rare disease as she was looking to commercialize her discovery. Schepartz says the mentoring she and her lab associates received has been invaluable. “The process taught us all how to think like entrepreneurs. It was a ton of fun.,” she says.