Abes Saïd, Ivanova Gabriela D, Abes Rachida, Arzumanov Andrey A, Williams Donna, Owen David, Lebleu Bernard, Gait Michael J
UMR 5235 CNRS, Université, Montpellier 2, Place Eugene Bataillon, 34095 Montpellier cedex 5, France.
Methods Mol Biol. 2009;480:85-99. doi: 10.1007/978-1-59745-429-2_6.
Several strategies based on synthetic oligonucleotides (ON) have been proposed to control gene expression. As for most biomolecules, however, delivery has remained a major roadblock for in vivo applications. Conjugation of steric-block neutral DNA mimics such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligonucleotides (PMO) to cell penetrating peptides (CPP) has recently been proposed as a new delivery strategy. It is particularly suitable to interfere sequence-specifically with pre-mRNA splicing thus offering various applications in fundamental research and in therapeutics. The chemical synthesis of these CPP conjugates as well as methodologies to monitor their cellular uptake and their efficiency in a reliable and easy to implement assay of splicing correction will be described.
人们已经提出了几种基于合成寡核苷酸（ON）的策略来控制基因表达。然而，与大多数生物分子一样，递送仍然是体内应用的主要障碍。最近有人提出将空间位阻中性DNA模拟物，如肽核酸（PNA）或磷酰二胺吗啉代寡核苷酸（PMO）与细胞穿透肽（CPP）缀合，作为一种新的递送策略。它特别适合于序列特异性干扰前体mRNA剪接，从而在基础研究和治疗学中有各种应用。将描述这些CPP缀合物的化学合成以及在可靠且易于实施的剪接校正测定中监测其细胞摄取及其效率的方法。
