Guiding protein delivery into live cells using DNA-programmed membrane fusion

Area of Science:

• Biotechnology
• Cell Biology
• Molecular Medicine

Background:

• Direct intracellular protein delivery is crucial for cell function manipulation and research but faces challenges due to limited efficient tools.
• Natural processes like SNARE-mediated membrane fusion offer efficient, targeted cargo delivery, inspiring new strategies.
• Current methods often struggle with endosomal entrapment, leading to protein degradation and reduced efficacy.

Purpose of the Study:

• To develop a novel strategy for efficient and controlled intracellular protein delivery into live cells.
• To leverage DNA hybridization for spatiotemporal control over liposome-cell membrane fusion.
• To demonstrate the functional delivery of exogenous proteins and their impact on cell fate.

Main Methods:

• A DNA-programmed membrane fusion strategy using protein-encapsulated liposomes.
• Utilizing DNA hybridization to control the fusion between liposomes and cell membranes.
• Delivering exogenous Cytochrome c into cells to assess functional outcomes.

Main Results:

• Achieved efficient intracellular protein delivery by bypassing the endosomal pathway.
• Demonstrated spatiotemporal control over liposome-cell membrane fusion via DNA programmability.
• Showcased functional delivery of Cytochrome c, which effectively regulated cell fate.

Conclusions:

• The DNA-mediated fusion strategy enables efficient, functional intracellular protein delivery.
• This approach offers precise spatiotemporal control, overcoming limitations of current methods.
• The strategy holds significant potential for protein-based therapeutics, regenerative medicine, and gene editing applications.