FDA fellow contributes to gene therapy research

Meet Susana Najera

Susana Najera grew up in a small community surrounded by nature, and science, technology, engineering and mathematics (STEM) were a constant presence in her life. Najera always had questions about her surroundings, technology and numbers, and she later decided to give some meaning and direction to those curiosities. She joined a robotics class in high school where she first learned how to build things that could help others. Ever since, Najera made an effort to participate in science and technology projects that can have a positive impact on someone’s life. During college, she became involved in clinical settings where she could see the effect that diseases had on individuals firsthand.

Susana Najera has turned her curiosities into the advancement of more efficient and affordable gene therapies with the U.S. Food and Drug Administration. (Photo Credit: Susana Najera)
Susana Najera has turned her curiosities into the advancement of more efficient and affordable gene therapies with the U.S. Food and Drug Administration. (Photo Credit: Susana Najera)

“At the University of California, San Diego, and the National Cancer Institute, I was able to meet some of the patients and their families that were affected by the diseases I was studying in lab, making my research more personal and putting a face to the cell lines I was generating in lab,” she said.

While studying for her master’s degree at Johns Hopkins University, Najera discovered the Oak Ridge Institute for Science and Education (ORISE) after listening to a speaker present about the Center for Biologics Evaluation and Research (CBER) Research Participation Training Program with the U.S. Food and Drug Administration (FDA). Najera applied and was accepted into the Mazor Lab in the Office of Therapeutic Products (OTP) at the Gene Therapy and Immunogenicity Branch.

The ORISE Research Participation Program at the FDA is an educational and training program designed to provide college students, recent graduates and university faculty opportunities to connect with the unique resources of the FDA. The CBER program provides temporary scientific training for participants having a background or interest in medical, biological, chemical, toxicological, mathematical, statistical or other related sciences.

As an ORISE participant at CBER, Najera is involved in two research projects that aim to develop safer and more efficacious therapies for patients. The first project focuses on identifying immunogenic peptides on the Adeno-associated virus (AAV) vector or the Cas9 transgene that activate human leukocyte antigen (HLA) class 1 responses. By identifying the peptides, scientists can deimmunize them and make AAV-Cas9 treatments safer for patients. Currently, the FDA has approved six AAV-based gene therapies and the first CRISPR-Cas9 therapy. This makes it critical that potential immunogenicity issues that could negatively impact safety or efficacy of the therapies are identified so strategies can be developed to address them.

Secondly, Najera is developing methods that are physiologically relevant for the testing of the efficacy and potency of AAV vectors. Manufacturing AAV is a limiting factor in AAV-based therapies because of its low yield and functional viral particles, so a method to enhance the production would allow for less expensive and more efficient AAV therapies.

“The way I approach this is either by screening libraries of peptides which we have found to be immunogenic through in silico models, engineering chimeric AAVs that are less likely to get detected by the immune system or by developing novel screening approaches that are more physiologically relevant than the current models, increasing the chances of quickly translating our discoveries to clinical applications,” she said. “One dose of AAV-based treatment could cost between 2-3 million dollars, but it’s a one and done kind of treatment.”

I’m proud to say everything I know now about the field and AAV treatments is because of this program and my appointment at OTP at CBER. This is the closest medicine and science has ever come to providing a cure to previously incurable diseases, and I’m proud to be part of this change."

Since the start of her appointment, Najera has been able to build on her previous experience in biochemistry and drug discovery by learning about gene therapy, virology and immunology. She recommends the program to any individual motivated by the application of science to real-life situations.

“I’m proud to say everything I know now about the field and AAV treatments is because of this program and my appointment at OTP at CBER,” she said. “This is the closest medicine and science has ever come to providing a cure to previously incurable diseases, and I’m proud to be part of this change,” she said.

Najera has co-authored an article titled “Rational immunosilencing of a promiscuous T-cell epitope in the capsid of an adeno-associated virus” that was published in the Nature Biomedical Engineering journal, and she is currently writing two manuscripts as a first author and two additional co-authored papers.

On top of her research, Najera is an active member of societies and mentoring programs aimed at encouraging young female scientists to stay involved and interested in STEM. She also serves on the board of directors at a community health clinic and a De Novo bank in Washington, D.C.

The CBER Research Participation Training Program is administered through ORISE under an agreement between the FDA and the U.S. Department of Energy (DOE). ORISE is managed for DOE by ORAU.