Crombez L, Charnet A, Morris M C, Aldrian-Herrada G, Heitz F, Divita G
Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, Department of Molecular Biophysics and Therapeutics, 1919 Route de Mende, 34293 Montpellier, France.
Biochem Soc Trans. 2007 Feb;35(Pt 1):44-6. doi: 10.1042/BST0350044.
The major obstacle to clinical development of siRNAs (short interfering RNAs), like for most of the nucleic-acid-based strategies, is their poor cellular uptake and bioavailability. Although several viral and non-viral strategies have been proposed to improve siRNA delivery, their applications in vivo remain a major challenge. We have developed a new strategy, based on a short amphipathic peptide, MPG, that is able to form stable nanoparticles with siRNA. MPG-based particles enter the cell independently of the endosomal pathway and can efficiently deliver siRNA in a fully biologically active form into a variety of cell lines and in vivo. This short review will discuss the mechanism and the potency of the MPG strategy for siRNA delivery both in vitro and in vivo.
与大多数基于核酸的策略一样，小干扰RNA（siRNA）临床开发的主要障碍是其较差的细胞摄取率和生物利用度。尽管已经提出了几种病毒和非病毒策略来改善siRNA的递送，但它们在体内的应用仍然是一个重大挑战。我们基于一种短的两亲性肽MPG开发了一种新策略，该肽能够与siRNA形成稳定的纳米颗粒。基于MPG的颗粒独立于内体途径进入细胞，并能以完全生物活性的形式将siRNA有效递送至多种细胞系和体内。这篇简短的综述将讨论MPG策略在体外和体内递送siRNA的机制和效力。
