Phosphorothioated DNA Engineered Liposomes as a General Platform for Stimuli-Responsive Cell-Specific Intracellular...

Area of Science:

• Biotechnology
• Nanomedicine
• Cellular Biology

Background:

• Intracellular protein delivery is crucial for protein drug-based cell therapy.
• Current methods lack specificity and efficiency in delivering proteins to target cell cytoplasms.
• Existing fusogenic liposome systems have limited cell-specific and controllable delivery capabilities.

Purpose of the Study:

• To design a novel system for cell-specific and controllable cytosolic protein delivery.
• To mimic viral fusion mechanisms for enhanced intracellular delivery.
• To overcome limitations of existing protein delivery technologies for cell therapy.

Main Methods:

• Development of a fusogenic liposome system modified with phosphorothioated DNA coatings.
• Design of a macromolecular fusion machine to dock liposomes to target cell membranes.
• Stimulation of membrane fusion using pH or UV light triggers for protein release.

Main Results:

• Demonstrated efficient cell-targeted delivery of proteins with varying sizes and charges.
• Confirmed the ability of phosphorothioated DNA coatings to facilitate spatial-temporally controlled protein delivery.
• Showcased the system's efficacy for both in vitro and in vivo applications.

Conclusions:

• The developed DNA-coated fusogenic liposome system offers a general strategy for targeted protein delivery.
• This approach enables precise control over protein release into specific cell populations.
• The technology holds significant potential for advancing protein drug-based cell therapies.