FDA Fellowship - Immunogenicity of Gene Editors

FDA Office and Location

A research opportunity is available in the Division of Plasma Protein Therapeutics (DPPT), Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA) in Silver Spring, Maryland.

The Center for Biologics Evaluation and Research (CBER) is one Center within the Food and Drug Administration, an Agency within the United States Government's Department of Health and Human Services. CBER's mission is to protect and enhance the public health through the regulation of biological and related products including blood, vaccines, allergenics, tissues, and cellular and gene therapies.

You will join a research program that broadly investigates unwanted immune responses to proteins used in therapeutic applications. The specific focus will be immune responses to Cas proteins used in gene editing. Cas9 proteins derived from human pathogens are the most extensively studied CRISPR-Cas gene editors. An important hurdle when developing and licensing a protein for clinical applications is the potential for immune responses to the protein.

We have previously demonstrated both T- and B-cell immunity to diverse Cas proteins. You will help identify promiscuous immunogenic epitopes in emerging Cas proteins and develop new tools to understand the safety consequences of immune responses to neo-epitopes generated due to off-target gene editing.

The following articles from our laboratory provide examples of research performed in our group:

• V.L. Simhadri, J.R. McGill, & Z.E. Sauna. Endotoxin contamination in commercially available Cas9 proteins potentially induces T-cell mediated responses. Gene Therapy. 2022
• V.L. Simhadri, L. Hopkins, J.R. McGill, B.R. Duke, S. Mukherjee, K. Zhang, & Z.E. Sauna. Cas9-derived peptides presented by MHC Class II that elicit proliferation of CD4(+) T-cells. Nat. Commun. 12: 5090, 2021
• J.R. McGill, O.N. Yogurtcu, H. Yang,
  
  D. Verthelyi, & Z.E. Sauna. Samp Pick:
  Selection of a cohort of subjects matching a population HLA distribution. Front. Immunol. 10: 2894, 2019
• V.L. Simhadri, J. McGill, S. McMahon, J. Wang, H. Jian & Z.E. Sauna. Prevalence of Pre-existing Antibodies to CRISPR-associated Nuclease Cas9 in the US Population. Mol Ther Methods Clin Dev. 10: 105-112, 2018.

Under the guidance of a mentor, you will receive training in cutting edge technologies directly relevant to promoting public health, opportunities to attend seminars and formal training programs. You will participate in collaborative projects with academia and/or industry and will thus be well positioned for diverse career options after the training period. Flexibility and a willingness to learn new techniques is a desirable quality in the applicant.

The mentor for this opportunity is Zuben

E. Sauna (zuben.sauna.gov). If you have questions about the nature of the research, please contact the mentor.

• Anticipated Appointment
  
  Start Date:
  
  2026. Start date is flexible and will depend on a variety of factors.
• Appointment Length:
  The appointment will initially be for one year, but may be renewed upon recommendation of FDA and is contingent on the availability of funds.
• Level of Participation:
  The appointment is full time.
• Participant Stipend:
  The participant will receive a monthly stipend commensurate with educational level and experience.

This opportunity is available to U.S. citizens, Lawful Permanent Residents (LPR), and foreign nationals. Non-U.S. citizen applicants should refer to the Guidelines for Non-U.S. Citizens Details page of the program website for information about the valid immigration statuses that are acceptable for program participation.

This program, administered by ORAU through its contract with the U.S. Department of Energy to manage the Oak Ridge Institute for Science and Education, was established through an interagency agreement between DOE and FDA. The participant will receive a monthly stipend commensurate with educational level and experience. Proof of health insurance is required for participation in this program. Participants do not become employees of FDA, DOE or the program…