Non-viral gene delivery with cationic polymers/nanoparticles relies on iterative optimization of the carrier to achieve delivery. Here we demonstrate, instead, that precision engineering of cell surfaces to covalently capture a polyplex accelerates gene delivery within just 10 min of exposure. Azides were installed into cell-surface sialic acids, which enabled the rapid and selective recruitment of cyclooctyne-functional polyplexes, leading to increased delivery of fluorescent cargo, and also increased plasmid expression and siRNA knockdown. Covalent delivery enhancement was also shown for a polymer-coated nanoparticle delivery system. This validates using cellular metabolic engineering (or other synthetic biology) tools to overcome payload delivery challenges.

This journal is © The Royal Society of Chemistry.

利用阳离子聚合物/纳米粒子进行非病毒基因传递依赖于递送载体的迭代优化。在这里，我们展示了通过精确工程化细胞表面以共价捕获聚复合物来加速基因传递的方法，在仅10分钟的暴露时间内即可实现。我们将叠氮基团安装到细胞表面的唾液酸中，从而能够快速且选择性地招募环辛炔官能化的聚复合物，这导致荧光货物递送量增加，并提高了质粒表达和siRNA敲除效率。还证明了一种聚合物包覆纳米粒子传递系统中的共价递送增强效果。这种方法验证了使用细胞代谢工程（或其他合成生物学）工具来克服有效载荷传递挑战的有效性。

注：该段落摘自某期刊，版权属于英国皇家化学学会。