Efficient gene delivery to immune cells via a recombinant multifunctional chimeric peptide nanocarrier: Implications in immunotherapy

Genetic modification of immune cells remains a major challenge in immunotherapy. While viral and non-viral carriers exist, low gene transfer efficiency persists with non-viral methods. We present a peptide-based carrier (MiRGD) for gene delivery to diverse immune cells. The MiRGD/plasmid complex formation was characterized via gel retardation, dynamic light scattering, and zeta potential analysis. After safety and efficiency optimization in HEK293T cells, MiRGD achieved 69 % chimeric antigen receptor (CAR) transfection in Jurkat T cells (>98 % viability) and 28 % in primary human T cells. Dendritic cells showed 61 % transfection with >85 % viability. In vivo, MiRGD functioned as a DNA vaccine against SARS-CoV-2, eliciting robust antibody titers, neutralization, and safe histopathology. These results demonstrate MiRGD's efficacy and biocompatibility for immune cell engineering (T cells, dendritic cells, macrophages) and vaccination, offering a cost-effective, non-toxic platform for immunotherapy applications.