Travirtide is a highly potent transduction enhancer for viral gene transfer. The peptide is designed to enhance transduction with various retroviral vectors. It promotes viral vector entry into mammalian cells via a rapid and robust protocol. Due to its high potency, it should find wide application in transduction experiments and has the potential to reduce the cost of CAR-T cell production.
Background of Viral Transduction Enhancers
Gene transfer into T cells, hematopoietic stem cells or other cells via viral vectors is a widely used technique in modern biology laboratories. It can be used in research projects, e.g. the validation of disease targets, as well as in the development of therapeutics for infectious diseases or cancer. One practical example are cellular immunotherapies involving T-cells with chimeric antigen receptors (CAR-Ts) or engineered T-cell receptors (TCR-Ts) have led to promising new cancer treatments. However, due to the complex manufacturing process, these therapies are still very costly. A critical step is gene transfer, which often relies on retroviral vectors and is often hampered by low transduction rates. To address this, a number of transduction enhancers have been developed, but with variable success1. These include surfactants, fibril-forming or amphipathic peptides2,3, and coating of cultureware4, which is cumbersome due to time-consuming liquid handling steps.
References
- Kaygisiz, K. et al., Materials promoting viral gene delivery. Biomater. Sci. (2020)
- Forssmann, W.G., Zgraja, A., Protransduzin-B, A gene transfer enhancer, WO2014177635A1.
- Fenard, D. et al., Vectofusin 1, a new viral entry enhancer, strongly promotes lentiviral transduction of human hematopoietic stem cells. Mol. Ther. Nucleic Acids (2013)
- Lamers, C. H, et al., Retronectin-assisted retroviral transduction of primary human T lymphocytes under good manufacturing practice conditions: tissue culture bag critically determines cell yield. Cytotherapy (2008)
Highly Potent Viral Transduction with Travirtide
Travirtide is a synthetic linear peptide that strongly enhances viral transduction, is well soluble and demonstrates low cytotoxicity. It is a potent enhancer of retroviral transduction, providing a >7-fold increase in transduction compared to the absence of enhancer at a concentration as low as 1.25 µg/mL. Travirtide is also significantly more potent than other transduction enhancers. For example, to achieve a strong transduction efficacy of >55 % GFP-positive cells, we needed a quarter of the amount of Travirtide compared to a well-known competitor product (1.25 vs. 5 µg/mL). At the same time, Travirtide was also more active than a second competitor product.
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