小干扰RNA
核酸
基因沉默
基因敲除
化学
RNA干扰
生物物理学
转染
细胞生物学
核糖核酸
生物化学
基因
生物
作者
Kevin Buyens,Martin Meyer,Ernst Wagner,Joseph Demeester,Stefaan C. De Smedt,Niek N. Sanders
标识
DOI:10.1016/j.jconrel.2009.08.026
摘要
To exploit the full therapeutic potential of short interfering RNA (siRNA), efficient delivery vehicles are needed as siRNA fails to enter cells spontaneously. Such carriers should also protect siRNA against degradation while it is on its way to the cytosol of the target cells. Cationic polymers are widely investigated as siRNA carriers. Cationic polymers and siRNA self-assemble into siRNA polyplexes which have been shown to silence genes in cell cultures. While siRNA polyplexes will become exposed to full blood after intravenous injection, in vitro gene knockdown is mostly evaluated in serum free media or media containing only a few percent of serum. Little knowledge is currently available on the stability of siRNA polyplexes in blood, while there are no methods available which allow a quantitative measurement of the disassembly of nucleic acid containing nanoparticles in such complex biological media. This paper shows that fluorescence fluctuation spectroscopy allows us to quantitatively monitor the disassembly of siRNA containing nanoparticles in full serum. It further shows that the gene silencing efficacy of siRNA polyplexes in serum containing media can be very well explained by their disassembling behavior in these media. Our findings are important for the further development of siRNA polyplexes and also other nanoparticulate nucleic acid delivery systems.
科研通智能强力驱动
Strongly Powered by AbleSci AI