Delivery of DNA ‐encoded vaccines and proteins in mice using cutaneous suction‐mediated transfection

A critical limitation of DNA vaccines and other therapeutics is transfection in vivo to produce the encoded antigens or therapeutic proteins. Cutaneous suction-based methods have demonstrated effectiveness in many animal models and have been successfully applied in human clinical trials, but have not been extended to mouse models, where numerous disease models, transgenic strains, and murine-specific reagents exist. Here, we establish and optimize methods for cutaneous suction-mediated DNA transfection in mice. By adapting a smaller cup diameter and smaller injection volume, the challenges of skin hyperelasticity and decreased skin thickness can be effectively addressed. Thus, we demonstrate that vaccinating mice with the GLS-5310 SARS-CoV-2 DNA vaccine using this method yields high levels of binding antibody and T-cell responses. Additionally, suction following injection of a novel pVAX1-based expression vector yielded systemic levels of a SEAP transgene. We conclude that suction-mediated delivery of nucleic acid-based therapies and vaccines can be a valuable tool for the study of preclinical mouse models.