Developing New Gene-Editing Techniques to Cure Disease

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

I was in high school in Medellín, Colombia, when I first decided that I wanted to become a genome engineer. I was mesmerized by the idea of modifying the blueprints of life and applying this ability to improve the world. I took part in several research opportunities during college and was one of 10 undergraduate students in Medellín to be awarded a prestigious research award by Medellín's Town Hall, which allowed me to apply to the Ph.D. Program at Mayo Clinic.

My Ph.D. research explored a new approach in gene editing, looking outside the genome that exists in the nucleus of the cell and focusing on the genome that exists in the mitochondria, the cellular structures that provide energy for the cell. My approach aims to make corrections in the mitochondrial genome, or mitochondrial DNA (mtDNA), a highly specialized and compact set of instructions that, among many other functions, enable mitochondria to serve as the powerhouses of the cell. In general, when genetic "typos" exist in either the nuclear or mitochondrial genome, they can be as apparently harmless as a misspelled word, or as alarming as an entire missing instruction, causing disease. The recently developed genome-editing technology CRISPR-Cas9 can address errors in nuclear DNA, but curative strategies for diseases caused by pathogenic genetic variants in mtDNA have yet to be developed.

In my research, I used molecular cloning to design and build synthetic DNA sequences that human cells can read, allowing them to produce functional proteins such as mtDNA base editors. Although a standard mtDNA base editing tool exists, it lacks precision to address the site where the most common pathogenic variant in human mtDNA occurs. In my work, I developed a more flexible, unconstrained base editor that can potentially target and precisely modify any of the sites in the mitochondrial genome. To measure the extent of these changes, I used both Sanger sequencing and next-generation sequencing, which provided detailed insights into the levels of mtDNA editing in the cells I worked with and showed that the new base editor outperformed the standard format. My study on these novel mtDNA editors, known as αDdCBEs, will facilitate the generation of new strategies to correct common pathogenic variants in human mtDNA. This work was featured on the cover of the journal Human Gene Therapy.

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

My experience at Mayo Clinic Graduate School of Biomedical Sciences prepared me exceptionally well for my future career by fostering a unique blend of scientific rigor and clinical relevance. The collaborative environment, alongside access to both cutting-edge research and patient care, strengthened my ability to approach complex biomedical problems with a focus on tangible, real-world outcomes. Additionally, Mayo's unique environment enabled me to pursue medical shadowing experiences, particularly in medical genetics, hematology and ophthalmology. These experiences gave me insight into patient care and helped me understand the implications of biomedical research, further reinforcing my commitment to translational science.