Department of Biomedical Engineering, University of California, Davis, CA, USA.
Biomater Sci. 2019 Jan 29;7(2):645-656. doi: 10.1039/c8bm01218k.
Gene therapy using viral vectors has been licensed for clinical use both in the European Union and the United States. Lentivectors (LV) and adeno-associated vectors (AAV) are two promising and FDA approved gene-therapy viral vectors. Many future applications of these vectors will benefit from targeting specific regions of interest within the body. Therefore, building on the early success of these vectors may depend on finding effective delivery systems to localize therapeutic administration. Degradable alginate hydrogels have been tested as appealing delivery vehicles for the controlled delivery of vector payloads. In this study, we compare the ability of two different degradable alginate hydrogel formulations to efficiently deliver LV and AAV. We propose that release rates of viral vectors are dependent on the physical properties of both the hydrogels and vectors. Here, we demonstrate that the initial strength and degradation rate of alginate hydrogels provides levers of control for tuning LV release but do not provide control in the release of AAV. While both alginate formulations used showed sustained release of both LV and AAV, LV release was shown to be dependent on alginate hydrogel degradation, while AAV release was largely governed by diffusive mechanisms. Altogether, this study demonstrates alginate's use as a possible delivery platform for LV and, for the first time, AAV - highlighting the potential of injectable degradable alginate hydrogels to be used as a versatile delivery tool in gene therapy applications.
基因治疗使用病毒载体已在欧盟和美国获得许可用于临床应用。慢病毒载体（LV）和腺相关病毒载体（AAV）是两种有前途且获得 FDA 批准的基因治疗病毒载体。这些载体的许多未来应用将受益于靶向体内特定的感兴趣区域。因此，在这些载体早期成功的基础上，可能取决于寻找有效的递药系统将治疗药物定位到特定部位。可降解藻酸盐水凝胶已被测试作为载体有效负载的控释的有吸引力的递药载体。在这项研究中，我们比较了两种不同的可降解藻酸盐水凝胶配方有效递送电镜和 AAV 的能力。我们提出，病毒载体的释放速率取决于水凝胶和载体的物理性质。在这里，我们证明藻酸盐水凝胶的初始强度和降解速率为 LV 释放提供了调节的控制手段，但不能控制 AAV 的释放。虽然使用的两种藻酸盐制剂都显示出 LV 和 AAV 的持续释放，但 LV 的释放被证明依赖于藻酸盐水凝胶的降解，而 AAV 的释放主要受扩散机制的控制。总的来说，这项研究表明藻酸盐可作为 LV 的一种可能的递药平台，并且首次证明了 AAV - 强调了可注射的可降解藻酸盐水凝胶作为基因治疗应用中多功能递药工具的潜力。
