Ultrasound‑targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3

Jin,Lifang; Li,Fan; Wang,Huiping; Li,Yunhua; Wei,Fang; Du,Lianfang

doi:10.3892/mmr.2013.1560

Ultrasound‑targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3

Authors:
- Lifang Jin
- Fan Li
- Huiping Wang
- Yunhua Li
- Fang Wei
- Lianfang Du
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Affiliations: Department of Ultrasound, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China, Experimental Research Center, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China
Published online on: June 27, 2013 https://doi.org/10.3892/mmr.2013.1560
Pages: 320-326
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Adeno‑associated virus (AAV) is a common vector utilized in gene therapy. The NIH/3T3 cell line, which is a potential induced pluripotent stem (iPS) cell type, was identified to be a less-permissive cell type to AAV due to its defective endosomal processing. Ultrasound‑targeted microbubble destruction (UTMD) enhanced the gene transduction of AAV in permissive cells. However, there are no data concerning UTMD enhancement in less-permissive cells, and the exact mechanism of UTMD enhancement in cellular uptake is unclear. Greater knowledge concerning the rate-limiting steps in NIH/3T3 cells would aid in the elucidation of the mechanism of UTMD enhancement in the gene transduction of AAV. In the present study, UTMD enhanced the gene transduction of AAV in NIH/3T3 cells, suggesting that UTMD‑enhanced AAV‑mediated gene transduction may be beneficial for gene therapy in iPS cells. The dose dependence of UTMD enhancement indicated that mechanisms other than sonoporation were involved in the cellular uptake of AAV. However, UTMD did not greatly increase the gene transduction of AAV in NIH/3T3 cells. Additionally, the similar degree of enhancement in the two cell types resulted in no correlation between UTMD and endosomal processing. Future studies on UTMD‑mediated AAV transduction in other non- or less‑permissive cell types may aid in elucidating the exact mechanism of UTMD enhancement in cellular uptake.

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