Ultrasound‑targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3.
Ultrasound‑targeted microbubble destruction enhances gene transduction of adeno-associated virus in a less-permissive cell type, NIH/3T3.
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超声靶向微泡破坏增强了腺相关病毒在不太许可的细胞类型 NIH/3T3 中的基因转导
DOI：
10.3892/mmr.2013.1560
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发表时间：
2013-08
影响因子：
3.4
通讯作者：
Du L
中科院分区：
文献类型：
--
作者：
Jin L;Li F;Wang H;Li Y;Wei F;Du L
腺相关病毒(AAV)是基因治疗中常用的载体。NIH/3T3细胞系是一种潜在的诱导多能干细胞(IPS)细胞类型，由于其内体加工缺陷，被鉴定为对AAV较不允许的细胞类型。超声靶向微泡破坏(UTMD)增强了AAV在允许细胞中的基因转导。然而，目前还没有关于UTMD在不允许的细胞中增强的数据，而且UTMD在细胞摄取中增强的确切机制尚不清楚。更多地了解NIH/3T3细胞中的限速步骤将有助于阐明UTMD增强AAV基因转导的机制。在本研究中，UTMD增强了AAV在NIH/3T3细胞中的基因转导，提示UTMD增强的AAV介导的基因转导可能有利于iPS细胞的基因治疗。UTMD增强的剂量依赖关系表明，细胞摄取AAV的机制不是声学作用。然而，UTMD并未显著增加AAV在NIH/3T3细胞中的基因转导。此外，两种细胞类型的增强程度相似，导致UTMD和内体处理之间没有相关性。未来对UTMD介导的AAV在其他非或不允许的细胞类型中的转导的研究可能有助于阐明UTMD增强细胞摄取的确切机制。
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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影响因子：
82.9
作者：
Qing, K;Mah, C;Srivastava, A
通讯作者：
Srivastava, A
影响因子：
2.9
作者：
Lioneiti, Vincenzo;Fittipaldi, Antonio;Picano, Eugenio
通讯作者：
Picano, Eugenio
影响因子：
5.4
作者：
Hansen, J;Qing, K;Srivastava, A
通讯作者：
Srivastava, A
影响因子：
2.9
作者：
Hauser, Joerg;Ellisman, Mark;Hauser, Manfred
通讯作者：
Hauser, Manfred
影响因子：
3.5
作者：
Bentes de Paula, Daisy Maria;Valero-Lapchik, Valderez Bastos;Han, Sang Won
通讯作者：
Han, Sang Won