Within a NSFC-DFG funded joint Sino-German collaboration between the group of Jie Song (Shanghai Jiao Tong University & Hangzhou Institute of Medicine) and our group, we investigated the use of circular single-stranded DNA as gene vectors. We found evidence that gene encoding single-strands are converted into double-stranded form inside mammalian cells and are then expressed. Notably, folding the CssDNAs using blocking strands in an origami-like fashion can inhibit gene expression, and blocked genes can be activated in cellulo by removing them with trigger strands via toehold-mediated strand displacement.
L. Tang, Z. Tian, J. Cheng, Y. Zhang, Y. Song, Y. Liu, J. Wang, P. Zhang, Y. Ke, F.C. Simmel, J. Song, Circular single-stranded DNA as switchable vector for gene expression in mammalian cells, Nat. Commun. 14, 6665 (2023).