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

Yuanli Li, Jue Wang, Celso Grebogi, Michael Foote, Feng Liu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Although known for its success in ameliorating muscle disorders, ultrasound (US)-mediated gene transfer in skeletal muscle has recently shown potential for treating a wide range of therapeutic applications. The disadvantages of the technique, however, including its relatively low transfer efficiency and toxic effects resulting in tissue damage, have impeded clinical progress. We describe a novel syringe-focused US device of our design that combines simultaneous DNA injection and US irradiation to resolve these issues, achieving improved DNA uptake for high expression and lowering the incidence of tissue injury.

Methods The novel, syringe-focused US device was used to introduce purified plasmid DNA encoding human neprilysin (hNEP) into mouse hindlimb skeletal muscle concurrent with US protocol (1.7MHz, 1 W/cm(2), 1-min exposure time). hNEP expression was measured in local skeletal muscle, blood serum and brain by immunoassay at different post-injection time points. The incidence of muscle fiber damage was subsequently assessed by Evans Blue dye (EBD) uptake using fluorescence microscopy.

Results The syringe-US device at the first time enabled simultaneous combination of DNA transfer and US stimulation gives rise to two months of gene expression of the encoded polypeptide as it is measured, at the same time as withstanding minor tissue damage. In addition, DNA injection without US treatment failed to induce hNEP expression.

Conclusions 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. Copyright (C) 2012 John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)54-61
Number of pages8
JournalThe Journal of Gene Medicine
Volume14
Issue number1
Early online date23 Jan 2012
DOIs
Publication statusPublished - Jan 2012

Keywords

  • ultrasound
  • gene transfer
  • naked DNA
  • neprilysin
  • skeletal muscle
  • tissue damage
  • skeletal-muscle
  • Alzheimers-Disease
  • amyloid burden
  • delivery
  • mouse
  • drug
  • brain
  • electrode
  • system

Cite this

A syringe-focused ultrasound device for simultaneous injection of DNA and gene transfer. / Li, Yuanli; Wang, Jue; Grebogi, Celso; Foote, Michael; Liu, Feng.

In: The Journal of Gene Medicine, Vol. 14, No. 1, 01.2012, p. 54-61.

Research output: Contribution to journalArticle

Li, Yuanli ; Wang, Jue ; Grebogi, Celso ; Foote, Michael ; Liu, Feng. / A syringe-focused ultrasound device for simultaneous injection of DNA and gene transfer. In: The Journal of Gene Medicine. 2012 ; Vol. 14, No. 1. pp. 54-61.
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AB - Background Although known for its success in ameliorating muscle disorders, ultrasound (US)-mediated gene transfer in skeletal muscle has recently shown potential for treating a wide range of therapeutic applications. The disadvantages of the technique, however, including its relatively low transfer efficiency and toxic effects resulting in tissue damage, have impeded clinical progress. We describe a novel syringe-focused US device of our design that combines simultaneous DNA injection and US irradiation to resolve these issues, achieving improved DNA uptake for high expression and lowering the incidence of tissue injury.Methods The novel, syringe-focused US device was used to introduce purified plasmid DNA encoding human neprilysin (hNEP) into mouse hindlimb skeletal muscle concurrent with US protocol (1.7MHz, 1 W/cm(2), 1-min exposure time). hNEP expression was measured in local skeletal muscle, blood serum and brain by immunoassay at different post-injection time points. The incidence of muscle fiber damage was subsequently assessed by Evans Blue dye (EBD) uptake using fluorescence microscopy.Results The syringe-US device at the first time enabled simultaneous combination of DNA transfer and US stimulation gives rise to two months of gene expression of the encoded polypeptide as it is measured, at the same time as withstanding minor tissue damage. In addition, DNA injection without US treatment failed to induce hNEP expression.Conclusions 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. Copyright (C) 2012 John Wiley & Sons, Ltd.

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