Abstract
The discovery of RNA interference (RNAi) as a naturally occurring mechanism for gene knockdown has attracted considerable attention toward the use of small interfering RNAs (siRNAs) for therapeutic purposes. Likewise, microRNAs (miRNAs) have emerged as important cellular regulators of gene expression, and their pathological underexpression allows for novel therapeutic strategies ('miRNA replacement therapy'). To address issues related to the instability, charge, and molecular weight of small RNA molecules, nanoparticle formulations have been explored for their in vivo application. Polyethylenimines (PEIs) are positively charged, linear, or branched polymers that are able to form nanoscale complexes with small RNAs, leading to RNA protection, cellular delivery, and intracellular release. This review highlights the important properties of various PEIs with regard to their use for in vivo RNA delivery. PEI modifications for increased efficacy, altered pharmacokinetic properties, improved biocompatibility and, upon covalent coupling of ligands, targeted delivery are described. An overview of various modified PEIs and a comprehensive list of representative studies using PEI-based siRNA or miRNA delivery in vivo are given.
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