Erythrocyte ghost-mediated gene delivery for prolonged and blood-targeted expression

Area of Science:

• Biotechnology
• Gene Therapy
• Nanomedicine

Background:

• Nonviral gene delivery systems are crucial for therapeutic applications.
• Achieving prolonged gene expression and targeted delivery remains a challenge.
• Erythrocyte ghosts (EG) offer potential as a biocompatible delivery vehicle.

Purpose of the Study:

• To evaluate erythrocyte ghosts (EG) as a nonviral delivery system for plasmid DNA.
• To assess the circulation time, expression levels, and targeting of EG-mediated gene delivery.
• To investigate the potential of EG for safe and prolonged blood-targeted gene therapy.

Main Methods:

• Plasmid DNA encoding murine interleukin-2 was loaded into erythrocyte ghosts (EG) via electroporation.
• The presence and integrity of plasmid DNA within EG were confirmed using fluorescence labeling.
• EG-mediated gene delivery was assessed in vivo following intravenous administration in mice.

Main Results:

• EG delivery resulted in a 92,000-fold higher level of plasmid DNA in blood compared to naked DNA at 21 minutes.
• Sustained and prolonged mRNA expression from plasmid DNA was observed in blood for up to 9 days post-injection.
• Gene expression was primarily targeted to blood cells, particularly granulocytes, with minimal distribution to other organs.

Conclusions:

• Erythrocyte ghosts (EG) serve as an effective, biocompatible, and nonviral delivery system for plasmid DNA.
• EG facilitate prolonged gene expression and exhibit specific targeting to blood cells.
• This approach demonstrates significant potential for developing safe and prolonged blood-targeted gene therapies.