Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection through Tail Vein

Area of Science:

• Gene Therapy
• Molecular Biology
• Hepatology

Background:

• Tail-vein injections are standard for mouse liver gene delivery using viral vectors or DNA.
• Conventional viral vector delivery uses low pressure/volume, while naked DNA requires high pressure/volume (hydrodynamic delivery).
• Vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped lentiviral vectors are effective but require optimized delivery methods.

Purpose of the Study:

• To compare the efficacy and specificity of different injection schemes for lentiviral vector delivery to the mouse liver.
• To evaluate conventional, primed, hydrodynamic, and intrahepatic injection methods.
• To optimize lentiviral gene transfer for enhanced liver targeting.

Main Methods:

• Comparison of four injection methods: conventional tail-vein, primed, hydrodynamic, and direct intrahepatic injections.
• Utilized in vivo bioluminescence imaging for reporter gene activity assessment.
• Analyzed liver sections from mice treated with GFP-encoding lentiviral vectors.

Main Results:

• Hydrodynamic injections demonstrated potent and targeted delivery of lentiviral vectors to the mouse liver.
• Achieved approximately 10-fold higher transduction rates compared to other methods.
• Successfully transduced around 80% of hepatocytes with GFP-encoding vectors.

Conclusions:

• Hydrodynamic tail-vein injections strongly augment lentiviral vector transfer to the mouse liver.
• This method reduces off-target delivery and achieves widespread hepatocyte transduction.
• Findings support more effective lentiviral gene delivery applications in mouse models.