A syringe‐focused ultrasound device for simultaneous injection of DNA and gene transfer

Li, Yuanli; Wang, Jue; Grebogi, Celso; Foote, Michael B.; Liu, Feng

doi:10.1002/jgm.1633

Cited by 4 publications

(5 citation statements)

References 27 publications

(28 reference statements)

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“…These issues may have been due to the defect of animal tolerance of APP/PS1 AD mice or very quick progression of AD pathology in the late stage of the disease, since we have previously shown that US-mediated hNEP gene transfer in vivo is safe in healthy mice and does not induce any complications. 30 Taken together, our nonviral hNEP delivery system via US combined with microbubbles may represent a potential approach for AD therapy. However, the half-life of NEP in vivo needs to be measured periodically over time in future studies.…”

Section: Discussionmentioning

confidence: 93%

“…Additionally, this finding also provided a possibility for NEP plasmid injected into peripheral skeletal muscle to be transferred to the brain for AD therapy. 30 Importantly, viral vectors for NEP gene delivery in vivo or in vitro in AD models may be associated with complications that would prevent the use of such a therapeutic strategy in humans. Thus, an efficient and safe NEP delivery system in vivo needs to be established for AD gene therapy in the future.…”

Section: Discussionmentioning

confidence: 99%

“…A syringe-focused US device was used according to a procedure that has been described previously. 30 Specifically, hNEP plasmids were prepared in microbubble suspensions that were then injected through the syringe simultaneously via US irradiation (1.7 MHz, 1.0 W/cm 2 , and a 1-min exposure time). After completion of the experiment, the whole US transducer and syringe device were removed together.…”

Section: Us Apparatusmentioning

confidence: 99%

“…This dose was determined to represent the optimal therapeutic dose in our previous studies. 30 Another experimental group of AD mice, as well as healthy C57BL mice, was not provided any treatments (no hNEP plasmid injections or US exposure). Finally, hNEP plasmid concentrations (typically 0.6 mg/mL) and purities (optical density: 260/280 nm ratios of 1.7-1.9) were evaluated by spectrophotometry.…”

Section: Us-mediated Gene Transfer Of Plasmid Hnep Into Skeletal Musclementioning

confidence: 99%

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Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD

Wang

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Amyloid b (Ab) accumulation in the brain is considered to be one of the major pathological changes in the progression of Alzheimer's disease (AD). Neprilysin (NEP) is a zinc metallopeptidase that efficiently degrades Ab. However, conventional approaches for increasing NEP levels or inducing its activation via viral-vector gene delivery have been shown to be problematic due to complications involving secondary toxicity, immune responses, and/or low gene transfer efficiency. Thus, in the present study, a physical and tractable NEP gene-delivery system via ultrasound (US) combined with microbubbles was developed for AD therapy. We introduced the plasmid, human NEP (hNEP), into skeletal muscle of 6-month-old amyloid precursor protein/presenilin-1 (APP/ PS1) AD mice. Interestingly, we found a significantly reduced Ab burden in the brain at 1 month after the delivery of overexpressed hNEP into skeletal muscle. Moreover, hNEP-treated AD mice exhibited improved performance in the Morris water maze compared to that of untreated AD mice. In addition, there were no apparent injuries in the injected muscle or in the lungs or kidneys at 1 month after the delivery of hNEP into skeletal muscle. These findings suggest that the introduction of hNEP into skeletal muscle via US represents an effective and safe therapeutic strategy for ameliorating AD-like symptoms in APP/PS1 mice, which may have the potential for clinical applications in the future.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Us Apparatusmentioning

confidence: 99%

Section: Us-mediated Gene Transfer Of Plasmid Hnep Into Skeletal Musclementioning

confidence: 99%

See 2 more Smart Citations

Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD

Wang

et al. 2020

Molecular Therapy - Methods & Clinical Development

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show abstract

“…However, this should be further clarified in an AD mouse model. Similarly, in another study that used focused ultrasound to introduce hNEP plasmid into the hindlimb of mice, hNEP protein in the skeletal muscle, brain tissue, and blood were detected by Western blotting and enzyme‐linked immunosorbent assay after 7, 14, and 30 days, and Evans blue staining of the injected muscle revealed only minor damage compared with conventional ultrasound transfection, and the injured tissue can recover over time (Li et al, ). These results demonstrate that nonviral methods are generally safer and more efficient for NEP delivery and may be adopted as a standard approach in AD therapy.…”

Section: Nonviral Delivery Of Nepmentioning

confidence: 96%

Neprilysin gene transfer: A promising therapeutic approach for Alzheimer's disease

Wang

Zhang

et al. 2015

J of Neuroscience Research

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Alzheimer's disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β (Aβ) in the neuropil and around blood vessels, and formation of neurofibrillary tangles. Aβ accumulation is considered the major pathological change in AD progression. In recent years, several therapeutic strategies for treating AD have focused on reducing the Aβ burden in the brain. Among these approaches, the expression of Aβ-degrading enzymes in the brain has been effective but, so far, impractical for treating patients. Neprilysin (NEP), the most prominent of the Aβ-degrading enzymes in vivo, has been successfully delivered intracranially by viral vectors and is a promising therapeutic approach for reducing Aβ accumulation and treating AD. However, some challenges are associated with the use of viral and nonviral vectors, including secondary toxicity, activation of the immune response, and low efficiency. Therefore, safe and efficient NEP delivery systems that could avoid the viral problems with minor injury and high transfection efficiency are required to deliver AD medical applications. This Mini-Review summarizes NEP gene transfer technologies that use viral and nonviral vectors and discusses the rationale and benefits of these delivery systems for AD treatment trials, providing a reference for basic and clinical studies on AD.

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Gene transfer to skeletal muscle by site-specific delivery of electroporation and ultrasound

Wang

Satterle

et al. 2012

Biochemical and Biophysical Research Communications

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A syringe‐focused ultrasound device for simultaneous injection of DNA and gene transfer

Abstract: This new technique provides a simple, safe and efficient nonviral gene delivery approach in skeletal muscle and shows promising applications for gene therapy of human disease, such as Alzheimer's disease.

Cited by 4 publications

References 27 publications

Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD

Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD

Neprilysin gene transfer: A promising therapeutic approach for Alzheimer's disease

Gene transfer to skeletal muscle by site-specific delivery of electroporation and ultrasound

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