Rational design for controlled release of Dicer-substrate siRNA harbored in phi29 pRNA-based nanoparticles.
Rational design for controlled release of Dicer-substrate siRNA harbored in phi29 pRNA-based nanoparticles.
复制标题
phi29 rna纳米颗粒中dicer底物siRNA控释的合理设计
DOI：
10.1016/j.omtn.2021.07.021
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发表时间：
2021-09-03
期刊：
影响因子：
--
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Binzel DW;Guo S;Yin H;Lee TJ;Liu S;Shu D;Guo P
自从2002年被《科学》杂志评为年度最佳突破以来，用于沉默基因和治疗疾病的小干扰RNA(SiRNA)一直是人们的梦想。随着FDA最近批准了四种基于siRNA的药物，RNA疗法成为药物开发的第三个里程碑的潜力已经成为现实。然而，RNA干扰(RNAi)治疗领域仍然面临着诸如靶向性、细胞内处理和靶向递送后的内体捕获等方面的挑战。包括在RNA纳米颗粒上的底物siRNA或许能够克服这些挑战。在这里，我们展示了基于PRNA的纳米颗粒可以被设计成在体外和体内有效地将DICER底物siRNA包埋到肿瘤细胞的胞浆中并释放siRNA。通过分子信标分析，对肿瘤细胞中DICER底物siRNAs的结构优化和化学修饰进行了评价。对悬垂的siRNA长度要求的研究表明，居民的手臂上至少需要23个核苷酸来加工骰子。上述序列参数和结构优化在最近的研究中得到证实，该研究表明基于PRNA的纳米颗粒能够释放功能性Survivin siRNA，用于在非小细胞肺癌、乳腺癌和前列腺癌动物模型中抑制肿瘤。用于沉默基因和治疗疾病的siRNA一直是一个流行的梦想，但并未完全实现。郭培轩及其同事报道了针对RNA纳米颗粒的siRNA的合理设计，从而在避免内小体的同时有效地输送，从而为RNA纳米颗粒上的siRNA设计提供了指南，以克服之前的障碍。
Small interfering RNA (siRNA) for silencing genes and treating disease has been a dream since ranking as a top Breakthrough of the Year in 2002 by Science. With the recent FDA approval of four siRNA-based drugs, the potential of RNA therapeutics to become the third milestone in pharmaceutical drug development has become a reality. However, the field of RNA interference (RNAi) therapeutics still faces challenges such as specificity in targeting, intracellular processing, and endosome trapping after targeted delivery. Dicer-substrate siRNAs included onto RNA nanoparticles may be able to overcome these challenges. Here, we show that pRNA-based nanoparticles can be designed to efficiently harbor the Dicer-substrate siRNAs in vitro and in vivo to the cytosol of tumor cells and release the siRNA. The structure optimization and chemical modification for controlled release of Dicer-substrate siRNAs in tumor cells were also evaluated through molecular beacon analysis. Studies on the length requirement of the overhanging siRNA revealed that at least 23 nucleotides at the dweller’s arm were needed for dicer processing. The above sequence parameters and structure optimization were confirmed in recent studies demonstrating the release of functional Survivin siRNA from the pRNA-based nanoparticles for cancer inhibition in non-small-cell lung, breast, and prostate cancer animal models. siRNA for silencing genes and treating diseases has been a popular dream but not fully realized. Peixuan Guo and colleagues report the rational design of siRNA to RNA nanoparticles for efficient delivery while avoiding endosomes, thus providing guidelines for siRNA design on RNA nanoparticles to overcome previous roadblocks.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
56.9
作者：
Chworos, A;Severcan, I;Jaeger, L
通讯作者：
Jaeger, L
影响因子：
12.4
作者：
Abdelmawla, Sherine;Guo, Songchuan;Li, Qi-Xiang
通讯作者：
Li, Qi-Xiang
影响因子：
56.9
作者：
Geary, Cody;Rothemund, Paul W. K.;Andersen, Ebbe S.
通讯作者：
Andersen, Ebbe S.
DOI：
10.1073/pnas.85.23.8998
发表时间：
1988-12-01
影响因子：
11.1
作者：
FROHMAN, MA;DUSH, MK;MARTIN, GR
通讯作者：
MARTIN, GR