FDA Fellowship - Immunogenicity of Gene Editors

Organization: U.S. Food and Drug Administration (FDA)

About the role

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.

Research Project

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. The research aims to:

• Identify promiscuous immunogenic epitopes in emerging Cas proteins.
• 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 the laboratory provide examples of research performed in the 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. SampPick: 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

Learning Objectives

Under the guidance of a mentor, you will receive training in cutting-edge technologies directly relevant to promoting public health. Opportunities include:

• Attending seminars and formal training programs.
• Participating in collaborative projects with academia and/or industry, positioning you for diverse career options after the training period.

Flexibility and a willingness to learn new techniques are desirable qualities in the applicant.

Mentor

The mentor for this opportunity is Zuben E. Sauna (zuben.sauna@fda.hhs.gov). For questions about the nature of the research, contact the mentor.

Appointment Details

• Start Date: 2026 (flexible, depending on various factors).
• Duration: Initially for one year, renewable upon recommendation and contingent on the availability of funds.
• Level of Participation: Full-time.
• Citizenship Requirements: Available to U.S. citizens, Lawful Permanent Residents (LPR), and foreign nationals. Non-U.S. citizen applicants should review the Guidelines for Non-U.S. Citizens for acceptable immigration statuses.

Qualifications

The qualified candidate should have received or be currently pursuing a master's or doctoral degree in one of the following fields:

• Immunology
• Biochemistry
• Biology
• Chemistry
• Bioinformatics
• Computational Biology
• Chemical Biology
• Pharmacy or Pharmaceutical Sciences

Degree must have been received within five years of the appointment start date or be currently pursuing with completion before the appointment start date.

Preferred Skills

• Experience in mammalian cell culture, cell-based assays, and flow cytometry.
• Experience in advanced techniques in immunology, biochemistry, molecular biology, or cell biology.
• Alternatively, a strong background in computational biology, modeling, or Machine Learning and Artificial Intelligence.
• Familiarity with basic techniques and principles in cell and molecular biology and biochemistry.
• Willingness to learn new technologies and methods and operate outside their comfort zone.