Pharmaceutical Biotechnology, Center of System-based Drug Research, Center for Nanoscience, Ludwig-Maximilians-University, Munich, Germany.
Mol Ther Nucleic Acids. 2012 Jan 31;1(1):e7. doi: 10.1038/mtna.2011.10.
Gene silencing mediated by small interfering RNA (siRNA) is a novel approach in the development of new cancer therapeutics. Polycations used for nucleic acid delivery still remain heterogeneous compounds, despite continuous progress in polymer synthetic technologies. Here we report the development of a structural defined folic acid polyethylene glycol (PEG) siRNA conjugate accessible via click chemistry yielding a monodisperse ligand-PEG-siRNA conjugate. The folic acid targeting ligand was synthesized by solid phase supported peptide chemistry. The conjugate was shown to be specifically internalized into folic acid receptor expressing cells. When combined with a structurally defined polycation, again synthesized with the precision of solid phase chemistry, efficient receptor specific gene silencing is achieved.
小干扰 RNA (siRNA)介导的基因沉默是开发新型癌症治疗方法的一种新方法。尽管聚合物合成技术不断取得进展，但用于核酸递送的聚阳离子仍然是异质化合物。在这里，我们报告了一种结构明确的叶酸聚乙二醇（PEG）siRNA 缀合物的开发，该缀合物可通过点击化学获得，生成单分散的配体-PEG-siRNA 缀合物。叶酸靶向配体通过固相支持的肽化学合成。该缀合物被证明可以特异性地被叶酸受体表达细胞内化。当与同样通过固相化学的精确性合成的结构明确的聚阳离子结合时，可实现有效的受体特异性基因沉默。
