DNA origami enables more precise targeting of extracellular vesicle therapies

Extracellular vesicles are tiny particles naturally released by cells, and they are increasingly being explored as delivery systems for drugs. Because they can carry proteins, RNA, and other molecules, they offer a promising way to deliver therapies directly to specific cells in the body. However, one of the biggest challenges has been controlling how these vesicles interact with target cells.

Scientists at the Hangzhou Institute of Medicine have developed a new method to improve how these delivery systems are engineered. Instead of randomly adding targeting molecules to the surface of extracellular vesicles, the team used a DNA-based structure to organize them with precision.

The approach uses a “cobweb” made from DNA origami, a technique where DNA is folded into specific shapes at the nanoscale. This cobweb structure sits on the surface of extracellular vesicle mimetics, which are engineered versions of natural vesicles, and allows scientists to control exactly where and how targeting ligands are placed.

This level of control is important because poorly arranged ligands can interfere with how vesicles bind to cells or even disrupt the vesicle’s natural functions. By carefully spacing these ligands, the researchers were able to fine tune how strongly the vesicles interact with target cells, improving uptake while avoiding unwanted interactions.

Another key advantage of this design is that it preserves important natural features of extracellular vesicles. For example, proteins like CD47 help vesicles avoid detection by the immune system. The DNA cobweb structure allows these proteins to remain functional, which can improve how long the vesicles circulate in the body.

Overall, this strategy provides a more controlled and efficient way to design extracellular vesicle-based therapies. It could help improve drug delivery in a range of applications, from cancer treatment to regenerative medicine, by ensuring that therapeutic cargo reaches the right cells with greater precision.