Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Nanomedicine (Lond). 2012 Apr;7(4):565-77. doi: 10.2217/nnm.12.28.
Nonviral delivery of nucleic acids is a potentially safe and viable therapeutic modality for inherited and acquired diseases. However, current systems have proven too inefficient for widespread clinical translation. The rational design of improved carriers depends on a quantitative, mechanistic understanding of the rate-limiting barriers to efficient intracellular delivery. Separation of the nucleic acid from the carrier is one of the barriers, which may be analyzed by Förster resonance energy transfer (FRET), a mechanism used to detect interactions between fluorescently labeled molecules. When applied to the molecular components of polymer or lipid-based nanocomplexes, FRET provides information on their complexation status, uptake, release and degradation. Recently, the design of FRET systems incorporating quantum dots as energy donors has led to improved signal stability, allowing prolonged measurements, as well as increased sensitivity, enabling direct detection and the potential for multiplexing. The union of quantum dots and FRET is providing new insights into the mechanisms of nonviral nucleic acid delivery through convergent characterization of delivery barriers, and has the potential to accelerate the design of improved carriers to realize the potential of nucleic acid therapeutics and gene medicine.
非病毒核酸递送是一种用于遗传性和获得性疾病的潜在安全且可行的治疗方式。然而，当前的系统在效率方面存在问题，无法广泛应用于临床转化。改进载体的合理设计取决于对有效细胞内递释的限速障碍的定量、机制理解。核酸与载体的分离是其中一个障碍，可以通过Förster 共振能量转移（FRET）来分析，这是一种用于检测荧光标记分子之间相互作用的机制。当应用于聚合物或脂质纳米复合物的分子成分时，FRET 提供了关于其络合状态、摄取、释放和降解的信息。最近，设计了将量子点作为能量供体的 FRET 系统，提高了信号稳定性，允许进行更长时间的测量，同时提高了灵敏度，实现了直接检测和潜在的多重检测。量子点和 FRET 的结合通过对递释障碍的收敛性特征分析，为非病毒核酸递释的机制提供了新的见解，并有可能加速改进载体的设计，以实现核酸治疗和基因医学的潜力。
