Finding DNA Molecules That Can Transport Drugs Inside Cells

What biomedical issue did you address in your research and what did your studies find?

My thesis project focused on developing a new way to get therapies, such as drugs, proteins and other helpful molecules, into the body's cells. Currently, there are few clinically tolerable delivery agents that can carry therapeutic molecules inside the cell and drop them at sites such as the nucleus or cytoplasm in an efficient manner. My project aimed to identify DNA molecules known as aptamers that have the ability to navigate the interior of a cell and deliver a specific therapy at a site where the cell can make use of it.

We tested pools of many trillions of randomly generated DNA aptamers and filtered them for unique functions, such as the ability to be taken up into cells, and then trafficked to a site inside the cell. Our process first required developing new chemical techniques that enabled us to separate aptamers at locations within the cell and identify whether the molecules reached their targets.

The project extended the work that I had begun as a post-baccalaureate researcher in the Graduate Research Education Program at Mayo. In that study, I had identified aptamers that could travel to the nucleus of cells but could not carry molecular cargo with them. During my Ph.D. research, we found several aptamers that were able to navigate to the inside of cells and be deposited into the cytoplasm. One aptamer we identified was capable of transporting an antibody across the outer membrane of the cell. To our knowledge, the antibody is the largest protein ever delivered to a specific location inside a cell by an aptamer. The study tested the limits of aptamer delivery and provided proof of concept that large proteins like antibodies can be transported. Because antibodies are used as therapies — in cancer, autoimmune diseases, transplant medicine, multiple sclerosis, gastric diseases and other areas — the ability to deliver functional antibodies to cells ultimately may expand the potential targets for antibody drugs.

What aspects of Mayo's culture helped you grow as a scientist and as a thinker?

What I have come to appreciate most about Mayo is the culture of collaboration. There are so many faculty here who are always willing to share knowledge, instruments, time and other resources that wind up enabling projects that couldn't be done without teamwork. Working on projects with labs that study topics outside of my expertise, such as neuroscience and cancer biology, has enabled me to learn in detail about fields I would never encounter without collaboration across groups or even across departments.

I'm a big believer in the idea that if you love your work, it won't often feel like work. This has always made academic research an easy choice for me, and I sincerely had a great time in graduate school. My advice to anyone else considering this path is to see if you find that intrinsic excitement within yourself, and if you do, pursue it.

What's next?

I'll be continuing my training as a postdoctoral fellow at Mayo to further this exciting avenue of research. My long-term goals are to become a faculty member at an academic institution and establish my own research lab.