Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305, USA.
Sci Rep. 2011;1:158. doi: 10.1038/srep00158. Epub 2011 Nov 15.
The accessibility of skin makes it an ideal target organ for nucleic acid-based therapeutics; however, effective patient-friendly delivery remains a major obstacle to clinical utility. A variety of limited and inefficient methods of delivering nucleic acids to keratinocytes have been demonstrated; further advances will require well-characterized reagents, rapid noninvasive assays of delivery, and well-developed skin model systems. Using intravital fluorescence and bioluminescence imaging and a standard set of reporter plasmids we demonstrate transfection of cells in mouse and human xenograft skin using intradermal injection and two microneedle array delivery systems. Reporter gene expression could be detected in individual keratinocytes, in real-time, in both mouse skin as well as human skin xenografts. These studies revealed that non-invasive intravital imaging can be used as a guide for developing gene delivery tools, establishing a benchmark for comparative testing of nucleic acid skin delivery technologies.
皮肤的可及性使其成为核酸治疗的理想靶器官；然而，有效的患者友好型递送仍然是临床应用的主要障碍。已经证明了多种有限的和低效的将核酸递送到角质形成细胞的方法；进一步的进展将需要特征明确的试剂、快速非侵入性的递送测定以及完善的皮肤模型系统。使用活体荧光和生物发光成像以及一组标准报告质粒，我们证明了使用皮内注射和两种微针阵列递送系统在小鼠和人异种移植皮肤中对细胞的转染。可以在实时检测到单个角质形成细胞中的报告基因表达，无论是在小鼠皮肤还是人皮肤异种移植中。这些研究表明，非侵入性活体成像可用于指导基因递送工具的开发，为比较核酸皮肤递送技术的测试建立基准。
