基于aavp的转基因传递固相转导基质:潜在的转化应用
An AAVP-based solid-phase transducing matrix for transgene delivery: potential for translational applications
原文发布日期:2017-05-26
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An AAVP-based solid-phase transducing matrix for transgene delivery: potential for translational applications
A hybrid vector of adeno-associated virus and phage (termed AAVP) has been introduced as a platform for systemic ligand-directed delivery of transgenes to tumors over the past decade. A series of studies have evaluated the AAVP platform for potential theranostic or purely therapeutic applications in several tumor models. Sufficient ligand-directed tumor targeting consistently resulted in specific molecular-genetic imaging and/or anti-tumor responses to ‘suicide’ transgene delivery. However, efforts to optimize transduction efficiency are still ongoing. Here, we set out to expand the translational utility of AAVP by combining it with gold (Au) nanoparticles in order to generate a ‘transducing matrix’ for improved targeted gene delivery in solid phase. Targeted AAVP-based solid-phase transduction is superior to conventional transduction in soluble (aqueous) environments. This transducing matrix is stable and can be further modified with additional attributes (for example, magnetization) for targeted imaging and therapeutic gene delivery. Notably, it spontaneously assembles around cells in vitro to markedly enhance transduction capabilities compared with AAVP alone. This versatile nanoplatform may enable new applications of AAVP for transgene delivery in translational settings including, for example, efforts toward complex tissue patterning.
在过去十年中,腺相关病毒-噬菌体杂交载体(AAVP)已被开发为一种系统性配体导向的转基因肿瘤靶向递送平台。一系列研究已在多种肿瘤模型中评估了AAVP平台用于诊疗一体化或纯治疗应用的潜力。充分的配体导向肿瘤靶向始终能够实现特异性分子遗传成像和/或针对"自杀"基因递送的抗肿瘤反应。然而, transduction效率的优化研究仍在持续进行。本研究旨在通过将AAVP与金纳米颗粒结合,构建一种用于增强固相靶向基因递送的"转导基质",从而扩展其转化应用潜力。基于AAVP的靶向固相转导效率显著优于传统液相(水相)环境中的转导方式。该转导基质结构稳定,并可进一步赋予其他功能特性(如磁化),用于靶向成像和治疗性基因递送。值得注意的是,在体外实验中该基质能自发围绕细胞组装,与单独使用AAVP相比显著增强转导能力。这种多功能纳米平台有望为AAVP在转化医学领域的转基因递送开辟新应用方向,例如推动复杂组织模式构建的研究。
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