Nitrous Oxide Enhances Focused Ultrasound Mediated Delivery of Viral Gene Therapy

Transcranial Magnetic Resonance Guided Focused Ultrasound (MRgFUS) can be used in conjunction with intravenous microbubbles to open the blood brain barrier (BBB) in discrete brain regions. This method is limited by the microbubble dose, the amount of energy that can be safely delivered across an intact skull, and the inability to target areas of the brain outside of central brain regions. We find that N2O administration substantially decreases the required dose of microbubbles and/or focused ultrasound pressure while still reliably opening the blood brain barrier. Additionally, we observe that the use of nitrous oxide improves the delivery of adeno-associated virus (AAV9) vector when compared to medical air. Our findings may help overcome focused ultrasound limitations and improve targeted delivery of therapeutics in humans. One Sentence SummaryNitrous Oxide potentiates Blood Brain Barrier opening with Focused Ultrasound and enhances viral vector delivery.