DNA nanotechnology has created a wide variety of nanostructures that provide a reliable platform for nanofabrication and DNA computing. However, constructing programmable finite arrays that allow for easy pre-functionalization remains challenge. We aim to create more standardized and controllable DNA origami components, which could be assembled into finite-scale and more diverse superstructures driven by instruction sets. In this work, we designed and implemented DNA origami building block pieces (DOBPs) with eight mutually independent programmable edges and formulated DNA instructions that tailored such components. This system enables DOBPs to be assembled into one or more specific 2D arrays according to the instruction sets. Theoretically, a two-unit system can generate up to 48 distinct DNA arrays. Importantly, experiments results demonstrated that DOBPs are capable of both deterministic and nondeterministic assemblies. Moreover, after examining the effects of different connection strategies and instruction implementations on the yield of the target structures, we assembled more complex 2D arrays, including limited self-assembly arrays such as ‘square frames’, ‘windmills’ and ‘multiples of 3’ long strips. We also demonstrated examples of Boolean logic gates ‘AND’ and ‘XOR’ computations based on these assembly arrays. The assembly system provides a model nano-structure for the research on controllable finite self-assembly and offers a more integrated approach for the storage and processing of molecular information.

Despite much-improved protocols that broadly suppress the adaptive immune cells, most allografts are still lost to chronic rejection, in which macrophages have been prominently featured in the graft. In both clinical and pre-clinical studies, the graft-infiltrating macrophages often acquire diverse effector activities, especially the M2-biased programs, to mediate graft damage. But the precise mechanisms that regulate such programs remain incompletely defined. In the present study, we took a genome-wide approach to profile the epigenomic changes of M2 polarized macrophages and uncovered the bromodomain and extra-terminal domain family protein-4 (BRD4) as a critical epigenetic regulator of M2 cells. Further in vitro studies revealed that either blocking BRD4 using a chemical inhibitor or conditional deletion of Brd4 in myeloid cells profoundly inhibited the induction of M2 cells. Moreover, in a fully MHC-mismatched heart transplant model, in which treatment with CTLA-4Ig led to the development of chronic rejection, inhibition of BDR4 in transplant recipients resulted in long-term heart allograft survival, which was associated with diminished intragraft M2 cells and absence of histological features of chronic rejection. Together, our data suggest that macrophages can be epigenetically modified in favor of transplant survival and that BRD4 seems a promising therapeutic target for blocking chronic allograft rejection.