Wyatt Kriebel – Developing AAV gene therapy for inherited ocular disease

Hi everyone! My name is Wyatt Kriebel and I am a rising junior who is majoring in Biology with a minor in chemistry and history with plans of attending medical school.

 As a person who has dealt with a health condition from a young age, I feel very passionate about my research to introduce new life-altering treatments to people who need them! I’m very proud to be a part of this program and be here with all of you, to see the fantastic projects each of us is working on and their eventual results!

In my off time, I enjoy fencing on the Pitt Fencing Team or tinkering on one of the four 3D-Printers to make fun like knick-knacks or useful everyday items. Recently I started growing my own little garden here on my roof which I enjoy tending to as a break from the chaos of life! Being from Reading PA, Pittsburgh has become my home away from home and as such, I also like to take the time to explore the city when I can and hike along trails just outside of Pittsburgh. 

AAV therapy

As for my research project this summer, I am a part of Dr. Leah Byrne’s ophthalmology lab researching gene therapies for inherited ocular diseases. I work with both her and a medical student at Pitt’s medical school, Alessandra Larimer-Picciani, in the development of adeno-associated virus (AAV)therapy in order to treat patients with a genetic disorder called Oculocutaneous Albinism. 

Patients with this disease have mutations in a specific gene, TYR, which is responsible for producing the tyrosinase protein. Tyrosinase produces melanin, a pigment found throughout the body, including the eye; the pigmentation within the eye is critical for protecting the back of the eye, known as the retina, from concentrated sunlight radiation. A cell population within the eye known as the retinal pigment epithelium (RPE) is a critical pigment-producing layer of the retina. Thus, melanin within the RPE  protects the retina by absorbing excess light rays enabling precise visual function. Because people with OCA have no protection against excess light due to the TYR mutation, they experience debilitating ocular effects including blindness and intense light sensitivity. 

The use of adeno-associated viral vector gene therapy (AAV gene therapy) is capable of delivering functional copies of the tyrosinase gene to the eye. Past studies have indicated that AAVs carrying the TYR gene have the potential to generate new, healthy tyrosinase enzymes that can produce pigment within the RPE. However, the most effective method of TYR-carrying AAV delivery for the treatment of OCA remains unknown. As such, the main goal of this project is to answer important questions surrounding the use of AAV therapy and its effectiveness in treating OCA. Previously designed gene therapies containing the TYR gene will be used to test the efficacy of gene transfer in a mouse model to determine the optimal delivery protocol for future clinical use.

This project shows promise given that the injection of AAVs will require minimal surgical intervention with local anesthesia which translates well to clinical use. AAV therapy has the potential to benefit the field of medicine and patients with OCA, but also public health by providing a crucial and new tool in fighting blindness.

Closing Remarks

The opportunity of the Brackenridge fellowship gives me the prospect to work with all of you from different fields since my research has wide-ranging applications for the medical world and the worlds of public health and sociology. By unlocking the foundations of gene therapy, we can start to treat populations that are disproportionately affected by genetic diseases and start the process of knocking down health barriers between different populations across our country and the world. And I hope with some help from all of you, we can start to break down the barrier that exists between most people and science.

Working with Dr. Byrne and med student Larimer-Picciani has given me a greater appreciation for medical research. As such, I plan on graduating in the Fall of 2022 and taking a gap year to fully commit myself to pursue research in the field of Ophthalmology with hopes of then getting accepted into the MD/Ph.D. program here at Pitt. I am passionate about the research I’m a part of and couldn’t imagine working on anything else. Developing treatment to restore vision in patients I feel is one of the biggest boosts in the quality of life that medicine could give a person and for that reason alone I am very proud to be working in this field!

Leave a Reply