Custom lipid-shelled microbubbles composed of DSEPC, DSPC and PEG-40 in PBS/EDTA, filled with perfluorobutane, form a stable 1.9–2.3 µm diameter population at 1–4×10^9 bubbles/ml. Plasmid DNA is affixed to their surfaces by brief vortexing, creating DNA-loaded carriers. A dual-transducer ultrasound platform combines low-power 14 MHz imaging with contrast pulse sequencing for real-time perfusion monitoring and a separate 1.3 MHz transducer (MI 1.6) to burst the microbubbles. Controlled bursts of 3–6 frames every 1–3 seconds, triggered upon perfusion confirmation, achieve localized DNA release and transfection. In vivo studies in murine tumor models have demonstrated efficient gene transfer and significant tumor growth inhibition.
Description
This technology stands apart through its tailored microbubble composition and hybrid ultrasound delivery. Unlike standard contrast agents, these bubbles are systematically optimized for high DNA-binding capacity without reliance on generic cationic lipids. The dual-frequency system uniquely enables simultaneous imaging and targeted destruction, with real-time feedback ensuring precise perfusion confirmation and bubble rupture. This combination of optimized shell chemistry and acoustic control yields superior spatiotemporal regulation of gene delivery, driving enhanced transduction efficiency in preclinical models.
Applications
- Targeted intravascular gene therapy
- Ultrasound-guided gene delivery
- Tumor-specific gene therapy
- Microbubble DNA delivery platform
- Real-time perfusion monitoring
Advantages
- Precise spatiotemporal control of gene release using dual-frequency ultrasound
- Real-time imaging of microbubble perfusion ensures accurate tumor targeting
- Optimized microbubble composition enhances DNA binding and acoustic responsiveness
- Minimally invasive intravascular delivery reduces off-target effects
- Demonstrated efficient in vivo tumor transduction and growth inhibition
IP Status
https://patents.google.com/patent/US11737971B2
