mRNA Delivery by a pH-Responsive DNA Nano-Hydrogel
mRNA Delivery by a pH-Responsive DNA Nano-Hydrogel
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通过 pH 响应 DNA 纳米水凝胶进行 mRNA 递送
DOI：
10.1002/smll.202101224
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发表时间：
2021-06-17
期刊：
影响因子：
13.3
通讯作者：
Zhu, Xiaoli
中科院分区：
文献类型：
--
作者：
Fu, Xin;Chen, Tianshu;Zhu, Xiaoli
递送mRNA来操纵蛋白质表达引起了广泛的关注，因为mRNA克服了转基因中的感染和突变风险问题，并且可以作为治疗疾病的药物。虽然目前已经有一些将mRNA递送到细胞内的载体，但它们在表达效率和生物相容性方面尚未达到良好的平衡。在这里，开发了一种用于 mRNA 递送的 DNA 纳米水凝胶系统。纳米水凝胶除目标mRNA外全部由DNA组成，因此与化学载体相比具有优越的生物相容性。同时，纳米水凝胶可以在精心设计的“X”形DNA支架和DNA接头的交联作用下被压缩成纳米球，从而通过胞吞作用将纳米水凝胶输送到细胞中。此外，通过将 pH 响应 i-motif 结构纳入纳米水凝胶中，可以实现 mRNA 的智能细胞内释放。因此，将有效的递送和释放结合起来，mRNA可以高效地翻译成相应的蛋白质，这与商业脂质体相当，但具有更好的生物相容性。由于优异的生物相容性和效率，这种纳米水凝胶系统有望成为体内传递功能性 mRNA 的有竞争力的替代品。
The delivery of mRNA to manipulate protein expression has attracted widespread attention, since that mRNA overcomes the problem of infection and mutation risks in transgenes and can work as drugs for the treatment of diseases. Although there are currently some vehicles that deliver mRNA into cells, they have not yet reached a good balance in terms of expression efficiency and biocompatibility. Here, a DNA nano-hydrogel system for mRNA delivery is developed. The nano-hydrogel is all composed of DNA except the target mRNA, so it has superior biocompatibility compared with those chemical vehicles. In parallel, the nano-hydrogel can be compacted into a nanosphere under the crosslinking by well-designed "X"-shaped DNA scaffolds and DNA linkers, facilitating the delivery into cells through endocytosis. In addition, smart intracellular release of the mRNA is achieved by incorporating a pH-responsive i-motif structure into the nano-hydrogel. Thus, taking the efficient delivery and release together, mRNA can be translated into the corresponding protein with a high efficiency, which is comparable to that of the commercial liposome but with a much better biocompatibility. Due to the excellent biocompatibility and efficiency, this nano-hydrogel system is expected to become a competitive alternative for delivering functional mRNA in vivo.