<i>In vivo</i> gene transfer into skeletal muscle of neonatal chicks by electroporation

Ijiri, Daichi; Saegusa, A.; Matsubara, Tomoko; Kanai, Yoshikatsu; Hirabayashi, Miho

doi:10.1111/j.1740-0929.2011.00983.x

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…The highly vascularized and stable nature of the skeletal muscle opens up opportunities for introducing gene-transfer agents into the systemic circulation for the treatment of human diseases distant from the site of muscle treatment. 28 For example, Liu et al 29 reported that expression of NEP in skeletal muscle using an adeno-associated virus (AAV) reduced Ab in a transgenic mouse model of AD. However, this previous study only measured NEP expression in injected local skeletal muscle but not in brain tissue.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

“…These findings demonstrate that peripheral expression of NEP, and likely other peptidases, represents an alternative to direct administration into the brain and illustrates the potential for using NEP expression in muscle for the prevention and treatment of AD (Liu et al, ). In particular, skeletal muscle cells, which are postmitotic and have longevity, allow the stable expression of injected plasmid DNA and can be safely and easily manipulated (Ijiri et al, ). Thus, this may become a promising strategy in the medical treatment of AD.…”

Section: Viral Vector‐mediated Nep Gene Therapy For Admentioning

confidence: 99%

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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In vivo gene transfer into skeletal muscle of neonatal chicks by electroporation

Cited by 2 publications

References 31 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

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