ArticleJournal of controlled release : official journal of the Controlled Release Society2018
Prolonging pulse duration in ultrasound-mediated gene delivery lowers acoustic pressure threshold for efficient gene transfer to cells and small animals.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Ultrasound-mediated targeted micro/nanobubbles: breaking new boundaries in precision tumor therapy.International journal of surgery (London, England) · 2026Article
- Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- mRNA Sonotransfection of Tumors with Polymeric Microbubbles: Co-Formulation versus Co-Administration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release.Ultrasonics sonochemistry · 2023Article
- Transcutaneous ultrasound-mediated gene delivery into canine livers achieves therapeutic levels of factor VIII expression.Blood advances · 2022Article
- Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice.Molecular therapy. Nucleic acids · 2022Article
- Ultrasound-targeted cationic microbubble-mediated gene transfection and inhibition of retinal neovascularization.International journal of ophthalmology · 2022Article
- Ultrasonic particles: An approach for targeted gene delivery.Advanced drug delivery reviews · 2021Review
- Synergies between therapeutic ultrasound, gene therapy and immunotherapy in cancer treatment.Advanced drug delivery reviews · 2021Review
- Recent Advances in Stimulus-Responsive Nanocarriers for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- A Comparison of Focused and Unfocused Ultrasound for Microbubble-Mediated Gene Delivery.Ultrasound in medicine & biology · 2021Article
- Enhanced Radiosensitization for Cancer Treatment with Gold Nanoparticles through Sonoporation.International journal of molecular sciences · 2020Article
- Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model.Molecular therapy. Methods & clinical development · 2019Article
- Ultrasound-Mediated Gene Therapy in Swine Livers Using Single-Element, Multi-lensed, High-Intensity Ultrasound Transducers.Molecular therapy. Methods & clinical development · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
While ultrasound-mediated gene delivery (UMGD) has been accomplished using high peak negative pressures (PNPs) of 2 MPa or above, emerging research showed that this may not be a requirement for microbubble (MB) cavitation. Thus, we investigated lower-pressure conditions close to the MB inertial cavitation threshold and focused towards further increasing gene transfer efficiency and reducing associated cell damage. We created a matrix of 21 conditions (n = 3/cond.) to test in HEK293T cells using pulse durations spanning 18 μs-36 ms and PNPs spanning 0.5-2.5 MPa. Longer pulse duration conditions yielded significant increase in transgene expression relative to sham with local maxima between 20 J and 100 J energy curves. A similar set of 17 conditions (n = 4/cond.) was tested in mice using pulse durations spanning 18 μs-22 ms and PNPs spanning 0.5-2.5 MPa. We observed local maxima located between 1 J and 10 J energy curves in treated mice. Of these, several low pressure conditions showed a decrease in ALT and AST levels while maintaining better or comparable expression to our positive control, indicating a clear benefit to allow for effective transfection with minimized tissue damage versus the high-intensity control. Our data indicates that it is possible to eliminate the requirement of high PNPs by prolonging pulse durations for effective UMGD in vitro and in vivo, circumventing the peak power density limitations imposed by piezo-materials used in US transducers. Overall, these results demonstrate the advancement of UMGD technology for achieving efficient gene transfer and potential scalability to larger animal models and human application.
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