My name is Sanjana Saravanan, and I received my bachelor’s degree in bioengineering from Oregon State University. During my undergrad career, I spent three years studying protein structure and dynamics in Dr. Elisar Barbar’s lab in the biochemistry/biophysics department at Oregon State University. My project involved characterizing the interactions between two cargo transport proteins that are critical for normal biological function. I am currently working with Dr. Amutha Boominathan at SENS Research Foundation. Our lab is focused on introducing engineered copies of mitochondrial protein-encoding genes into the nuclear genome in order to rescue mutations in the mitochondrial DNA. The team has been successful in expressing all thirteen proteins encoded by mitochondrial DNA and is working on optimizing several parameters necessary for successful protein targeting, transport and integration.

Thirteen of the genes in mitochondrial DNA code for proteins in the oxidative phosphorylation (OxPhos) relay, a process that is crucial for metabolism and cellular respiration. Mutations in these genes accumulate with age and can lead to a wide variety of diseases. Recently, a form of gene therapy that directly addresses mitochondrial DNA mutations has emerged as a therapeutic for mitochondrial diseases. This involves inserting the mitochondrial gene coding for the OxPhos protein into the nuclear genome so that it is translated in the cytoplasm. The idea is that introducing a version of the gene without the mutation and synthesizing the proteins using the nuclear translation system will rescue lost function and reverse the symptoms of disease. My project is specifically looking at a mutation in a subunit of the first OxPhos protein complex. This mutation causes a disease called Leber’s Hereditary Optic Neuropathy (LHON) which is characterized by major loss of vision.

Several labs have already shown that this form of gene therapy works in the context of the LHON mutation and is able to reverse vision loss temporarily. The most notable drawbacks to the gene therapy in clinical trial for LHON are that vision loss returns after several months and their method of allotopic expression does not permanently integrate the corrected gene in the patient’s genome. We have been using a version of the gene that is different than the one being using in a clinical trial that will potentially improve the ability of the cell to generate and integrate the protein into the OXPHOS complex. Our lab has also been working on a way to make sure the correct version of the gene is integrated into the nuclear DNA to be copied and translated from the nucleus for a long-term solution.