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Background Cellular immunotherapies using genetically reprogrammed immune cells, such as T-lymphocytes with chimeric antigen receptors (CAR-Ts) or engineered T-cell receptors (TCR-Ts), have led to promising new treatments for hematological malignancies. However, due to the complex multi-step manufacturing process, these therapies are still very costly. A crucial step is the gene transfer, which often relies on retroviral vectors and is frequently associated with low transduction rates. To address this limitation, a range of transduction enhancers and protocols have been developed, however, with variable success. These include surfactants, fibril-forming or amphipathic peptides such as Protransduzin-B and Vectofusin-1, and coating of cultureware with recombinant fibronectin (or fragments thereof), which is cumbersome due to time consuming liquid handling steps.Methods Here we describe the novel transduction enhancer Travirtide. We discovered Travirtide, a 12-meric linear peptide, through rational medicinal chemistry optimization cycles starting from known fibril-forming peptides. It was characterized and compared to known transduction enhancers using the following assays: transduction efficacy was determined by measuring%GFP expression after transduction of Jurkat T-cells with a GFP encoding gamma-retroviral vector; aqueous solubility was determined by an HPLC based method; and cytotoxicity was assessed with a Resazurin-based assay.Results Travirtide exhibited higher transduction efficacy than the commonly used transduction enhancers Protransduzin-B and Vectofusin-1. Additionally, it demonstrated high aqueous solubility and, also very important, lower cytotoxicity compared to both aforementioned reagents.Conclusions In conclusion, Travirtide is a highly potent novel transduction enhancer with very low cytotoxicity. Due to its strong potency it should find wide application in transduction experiments and has the potential to reduce CAR-T cell production costs, thus representing a significant step towards more affordable cellular therapies.