Duplex end breathing determines serum stability and intracellular potency of siRNA-Au NPs.
Duplex end breathing determines serum stability and intracellular potency of siRNA-Au NPs.
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DOI：
10.1021/mp200084y
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发表时间：
2011-08-01
影响因子：
4.9
通讯作者：
Mirkin CA
中科院分区：
文献类型：
--
作者：
Patel PC;Hao L;Yeung WS;Mirkin CA
研究了siRNA功能化的金纳米颗粒（siRNA-Au NPs）用于Dicer识别和血清稳定性的结构要求。我们发现，这些颗粒的核酸上的3′突出端优先被Dicer识别，但也使siRNA双链体更容易受到非特异性血清降解。Dicer和血清核酸酶对平端双链体的偏好低于3′端突出的双链体。重要的是，用具有相对较少的热呼吸的钝双链体官能化的金纳米颗粒对血清降解的稳定性高达15倍，而不损害Dicer识别。这种增加的稳定性导致siRNA-Au NP的细胞摄取增加300%并改善基因敲除。
Structural requirements of siRNA-functionalized gold nanoparticles (siRNA-Au NPs) for Dicer recognition and serum stability were studied. We show that the 3′ overhang on the nucleic acids of these particles is preferentially recognized by Dicer but also makes the siRNA duplexes more susceptible to non-specific serum degradation. Dicer and serum nucleases show lower preference for blunt duplexes as opposed to those with 3′ overhangs. Importantly, gold nanoparticles functionalized with blunt duplexes with relatively less thermal breathing are up to 15 times more stable against serum degradation without compromising Dicer recognition. This increased stability leads to a 300% increase in cellular uptake of siRNA-Au NPs and improved gene knockdown.
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