Abstract
Ultrasound (US) has been found to facilitate the transport of DNA across cell membranes. However, the transfection efficiency is generally low, and the expression duration of the transfected gene is brief. In this study, a tertiary polycation, Poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA), was used as a carrier for US-mediated gene transfection. Its in-vitro and in-vivo effects on the transfection efficiency and the expression duration were evaluated. A mixture of pCI-neo-luc and PDMAEMA was transfected to cultured cells or mouse muscle by exposure to 1-MHz pulse US. A strong expression of luciferase was found 10 days after the transfection in vitro regardless of US exposure. However, effective transfection only occurred in the US groups in vivo. The transfection ability depended on the weight ratio of PDMAEMA to DNA, and was different for the in-vitro and in-vivo conditions. Lower weight ratios, e.g., 0.25, exhibited better in-vivo expression for at least 45 days.
Highlights
Gene therapy has been shown to have great potential to overcome the drawbacks associated with conventional drug and protein therapeutic regimens for a range of diseases such as inherited immune deficiencies, cardiovascular disease, and cancer
The molecular weight of the prepared Poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) polycation was determined by aqueous gel-permeation chromatography (GPC), using two Viscogel columns, a G4000 PWXL and a G6000 PWXL connected to a model Viscotec refractive-index detector at a flow rate of 1.0 mL/min and a column temperature of 23uC
To understand the physicochemical properties of the PDMAEMA/DNA nanoparticles used in all experiments, their particle sizes and zeta-potentials were evaluated and compared
Summary
Gene therapy has been shown to have great potential to overcome the drawbacks associated with conventional drug and protein therapeutic regimens for a range of diseases such as inherited immune deficiencies, cardiovascular disease, and cancer. Viral vectors have been predominantly used for gene therapy due to their ease of use and high efficiency. Several issues related to safety and immunogenicity have restricted the clinical application of viral vectors [1,2]. Among the non-viral vectors, USmediated gene transfer has recently received considerable attention [4,5,6,7,8,9]. Many of the desired characteristics of gene therapy, including low immunogenicity, minimal invasiveness, site specificity, and safety for repeated treatments could be realized by applying the US transfer technique with microbubbles.[8,10,11,12,13]
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