Universal DNA-Based Sensing Toolbox for Programming Cell Functions.

By recombining natural cell signaling systems and further reprogramming cell functions, use of genetically engineered cells and bacteria as therapies is an innovative emerging concept. However, the inherent properties and structures of the natural signal sensing and response pathways constrain further development. We present a universal DNA-based sensing toolbox on the cell surface to endow new signal sensing abilities for cells, control cell states, and reprogram multiple cell functions.

A DNA Nanodevice-Based Platform with Diverse Capabilities.

Social biotic colonies often perform intricate tasks by interindividual communication and cooperation. Inspired by these biotic behaviors, a DNA nanodevice community is proposed as a universal and scalable platform. The modular nanodevice as the infrastructure of platform contains a DNA origami triangular prism framework and a hairpin-swing arm machinery core.

Nano-Biohybrid DNA Engager That Reprograms the T-Cell Receptor.

Although engineered T cells with transgenic chimeric antigen receptors (CARs) have made a breakthrough in cancer therapeutics, this approach still faces many challenges in the specificity, efficacy, and self-safety of genetic engineering. Here, we developed a nano-biohybrid DNA engager-reprogrammed T-cell receptor (EN-TCR) system to improve the specificity and efficacy, mitigate the excessive activation, and shield against risks from transgenesis, thus achieving a diversiform and precise control of the T-cell response. Utilizing modular assembly, the EN-TCR system can graft different specificities on T cells via antibody assembly.

An miRISC-initiated DNA nanomachine for monitoring MicroRNA activity in living cells.

MicroRNAs (miRNAs) play an important role in post-transcriptional regulation of gene expression. However, methods to accurately detect miRNA activity in living cells are still limited. Here we developed a DNA nanomachine initiated by a miRNA-induced silencing complex (miRISC) for imaging miRNA activity in living cells.

Catalytic-Hairpin-Assembly-Assisted DNA Tetrahedron Nanoprobe for Intracellular MicroRNA Imaging.

The aberrant expression levels of microRNAs (miRNAs) are tightly linked with the initiation and development of various diseases and genetic disorders. Here, we reported a catalytic-hairpin-assembly-assisted DNA tetrahedron nanoprobe for intracellular miRNA detection. The target miRNA initiated the catalytic-hairpin-assembly reaction between the tetrahedron nanoprobes to generate large tetrahedron clusters with an enhanced fluorescence resonance energy transfer between the Cy3 and Cy5 dyes.

Multimachine Communication Network That Mimics the Adaptive Immune Response.

Biological organisms capable of controlling and performing a wide variety of functions have inspired attempts to mimic biological systems with designable intelligence. Here we develop a multimachine communication network (MMCN) to mimic the operation and function of adaptive immune response (AIR) via connecting three kinds of DNA machines built from module-functionalized gold nanoparticles. These machines simulate three critical immune cells, dendritic cells, T and B lymphocytes, and their differentiation and coordinated interaction upon exposure and response to an invading pathogen.

A highly integrated DNA nanomachine operating in living cells powered by an endogenous stimulus.

Synthetic molecular machines have received increasing attention because of their great ability to mimic natural biological motors and create novel modes of motion. However, very few examples have been implemented with real autonomous movement inside living cells, due to the challenges of the driving force and highly integrated system design. In this work, we report an elegant, highly integrated DNA nanomachine that can be powered by endogenous ATP molecules and autonomously operated inside living cells without any auxiliary additives.

Rational Engineering of a Dynamic, Entropy-Driven DNA Nanomachine for Intracellular MicroRNA Imaging.

We rationally engineered an elegant entropy-driven DNA nanomachine with three-dimensional track and applied it for intracellular miRNAs imaging. The proposed nanomachine is activated by target miRNA binding to drive a walking leg tethered to gold nanoparticle with a high density of DNA substrates. The autonomous and progressive walk on the DNA track via the entropy-driven catalytic reaction of intramolecular toehold-mediated strand migration leads to continuous disassembly of DNA substrates, accompanied by the recovery of fluorescence signal due to the specific release of a dye-labeled substrate from DNA track.