The researchers wanted to know if blocking the HoxA1 gene could reverse cancer in lab-grown cells from mouse milk ducts. Amy Brock, Ph.D., a former Wyss Institute postdoctoral fellow who is now an Assistant Professor of Biomedical Engineering at the University of Texas, Austin, grew healthy mouse or human mammary-gland cells in a nutrient-rich, tissue-friendly gel. Healthy cells ensconced in the gel formed hollow spheres of cells akin to a normal milk duct. But cancerous cells, in contrast, packed together into solid, tumor-like spheres.
Brock treated cancerous cells with a short piece of RNA called a small interfering RNA (siRNA) that blocks only the HoxA1 gene. The cells reversed their march to malignancy, stopping their runaway growth and forming hollow balls as healthy cells do. What's more, they specialized as if they were growing in healthy tissue.
The siRNA treatment also stopped breast cancer in a line of mice genetically engineered to have a gene that causes all of them to develop cancer. The Wyss team worked with Michael Goldberg, Ph.D., Assistant Professor of Microbiology and Immunobiology at Harvard Medical School and the Dana-Farber Cancer Institute, to leverage a novel method he had developed to deliver the siRNA efficiently.
They packed the siRNA into nanoparticles called lipidoids that allow for genes to be silenced for weeks inside the body. They then did something unusual: they injected these nanoparticles directly through the nipples into the milk ducts of the cancer-prone mice, using a new method that Silva Krause, Ph.D., a postdoctoral fellow on Ingber's team, had developed. This is important because the cells that line the ducts are the ones that form breast tumors in mice as well as humans.
Weeks went by as Brock and Krause watched. The treated mice remained healthy, while untreated mice developed breast cancer. "There was no aha moment,"
|Contact: Dan Ferber|
Wyss Institute for Biologically Inspired Engineering at Harvard