A DNA origami-based enzymatic cascade nanoreactor for chemodynamic cancer therapy and activation of antitumor immunity.

Chemodynamic therapy (CDT) is a promising and potent therapeutic strategy for the treatment of cancer. We developed a DNA origami-based enzymatic cascade nanoreactor (DOECN) containing spatially well-organized Au nanoparticles and ferric oxide (FeO) nanoclusters for targeted delivery and inhibition of tumor cell growth. The DOECN can synergistically promote the generation of hydrogen peroxide (HO), consumption of glutathione, and creation of an acidic environment, thereby amplifying the Fenton-type reaction and producing abundant reactive oxygen species, such as hydroxyl radicals (•OH), for augmenting the CDT outcome.

Mesenchymal Stem Cells Engineered by Multicomponent Coassembled DNA Nanofibers for Enhanced Wound Healing.

A major challenge for stem cell therapies, such as using mesenchymal stem cells to treat skin injuries, is the stable engraftment of exogenous cells and the maintenance of their regenerative capacities in the wound areas. DNA-based self-assembly strategies can be used for artificial and multifunctional cell surface engineering to stabilize and enhance their functions for therapeutic applications. Here, we developed DNA nanofiber-decorated stem cells, in which DNA-based, multivalent fiber-like structures were self-assembled in situ on the cell surfaces.

Toward Unified AI Drug Discovery with Multimodal Knowledge.

In real-world drug discovery, human experts typically grasp molecular knowledge of drugs and proteins from multimodal sources including molecular structures, structured knowledge from knowledge bases, and unstructured knowledge from biomedical literature. Existing multimodal approaches in AI drug discovery integrate either structured or unstructured knowledge independently, which compromises the holistic understanding of biomolecules. Besides, they fail to address the missing modality problem, where multimodal information is missing for novel drugs and proteins.

A DNA Origami-Based Gene Editing System for Efficient Gene Therapy in Vivo.

DNA nanostructures have played an important role in the development of novel drug delivery systems. Herein, we report a DNA origami-based CRISPR/Cas9 gene editing system for efficient gene therapy in vivo. In our design, a PAM-rich region precisely organized on the surface of DNA origami can easily recruit and load sgRNA/Cas9 complex by PAM-guided assembly and pre-designed DNA/RNA hybridization.

Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.

Patient-derived tumor organoids (PDOs) have emerged as a reliable in vitro model for drug discovery. However, RNA sequencing-based analysis of PDOs treated with drugs has not been realized in a high-throughput format due to the limited quantity of organoids. Here, we translated a newly developed pooled RNA-seq methodology onto a superhydrophobic microwell array chip to realize an assay of genome-wide RNA output unified with phenotypic data (Grouped-seq).

Nanoliter Centrifugal Liquid Dispenser Coupled with Superhydrophobic Microwell Array Chips for High-Throughput Cell Assays.

Microfluidic systems have been regarded as a potential platform for high-throughput screening technology in drug discovery due to their low sample consumption, high integration, and easy operation. The handling of small-volume liquid is an essential operation in microfluidic systems, especially in investigating large-scale combination conditions. Here, we develop a nanoliter centrifugal liquid dispenser (NanoCLD) coupled with superhydrophobic microwell array chips for high-throughput cell-based assays in the nanoliter scale.