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Updated: Jul 16, 2025
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Focused Ultrasound Induced Blood-Brain Barrier Opening for Targeting Brain Structures and Evaluating Chemogenetic Neuromodulation
Published on: December 22, 2020
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Acoustically targeted noninvasive gene therapy in large brain volumes
Shirin Nouraein1,2,3, Sangsin Lee1,2, Vidal A Saenz1
1Department of Bioengineering, Rice University, Houston, TX, 77030, USA.
Gene Therapy
|September 11, 2023
Summary
Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) enables efficient, brain-wide gene delivery for genetic disorders. Multi-site FUS-BBBO achieved high transduction rates and effective gene editing, demonstrating its therapeutic potential.
Area of Science:
- Neuroscience
- Gene Therapy
- Biotechnology
Background:
- Genetic brain disorders often affect widespread brain regions, posing challenges for localized treatments.
- Adeno-associated viral vectors (AAVs) are promising for treating these disorders, but efficient delivery to large brain areas is difficult.
- Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) offers a noninvasive method for AAV delivery.
Purpose of the Study:
- To evaluate the efficiency and safety of multi-site FUS-BBBO for brain-wide gene delivery.
- To assess the impact of increasing targeted sites on transduction efficiency.
- To demonstrate the application of multi-site FUS-BBBO for gene editing in large brain volumes.
Main Methods:
- Simultaneously opening up to 105 sites using FUS-BBBO.
- Delivering adeno-associated viral vectors (AAVs) to targeted brain regions.
- Evaluating gene delivery efficiency, transduction rates, and safety parameters (animal weight, neuronal loss).
- Implementing CRISPR/Cas9 gene editing following FUS-BBBO.
Main Results:
- Increasing the number of targeted sites enhanced gene delivery efficiency.
- Achieved transduction of up to 60% of brain cells with comparable efficiency across most brain regions.
- Demonstrated safe gene delivery even with 105 simultaneous targeted sites, with no adverse effects on animal weight or neuronal loss.
- Successfully performed gene editing using CRISPR/Cas9, though some neuronal loss was observed at targeted sites.
Conclusions:
- Multi-site FUS-BBBO offers a synergistic effect, significantly improving transduction efficiency for brain-wide gene delivery.
- This study provides the first demonstration of large brain volume gene editing via noninvasive FUS-BBBO.
- FUS-BBBO is a safe and effective platform for delivering gene therapies to extensive brain areas, paving the way for treating widespread genetic brain disorders.
