德国柏林洪堡大学Christian P. R. Hackenberger团队报道了细胞表面反应性细胞穿透肽添加剂促进大分子生物分子的细胞摄取。相关研究成果于2021年4月15日发表于国际顶尖学术期刊《自然—化学》。

实现功能蛋白的细胞传递和细胞内生物利用率是生命科学面临的重大挑战。

该文中，研究人员证明了即使在低微摩尔浓度下，硫醇反应性富含精氨酸的肽添加剂可以在非内吞模式下增强细胞对蛋白质-CPP结合物的摄取。研究人员发现这种硫醇或HaloTag反应性添加剂可以在细胞表面形成共价锚定的CPPs，这种CPPs可以高效地协同传递蛋白质。

研究表明，利用最有效CPP添加剂的硫醇反应性，通过简单的共添加少量过量的CPP，含Cys的蛋白质可以很容易地被输送到细胞质中。此外，研究人员还展示了“CPP添加剂技术”在功能酶、纳米体和全长免疫球蛋白G抗体传递中的应用。

新的细胞摄取方案大大简化了蛋白质和抗体传递的可及性和效率，只需最少的化学或基因工程。

附：英文原文

Title: Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives

Author: Anselm F. L. Schneider, Marina Kithil, M. Cristina Cardoso, Martin Lehmann, Christian P. R. Hackenberger

Issue&Volume: 2021-04-15

Abstract: Enabling the cellular delivery and cytosolic bioavailability of functional proteins constitutes a major challenge for the life sciences. Here we demonstrate that thiol-reactive arginine-rich peptide additives can enhance the cellular uptake of protein–CPP conjugates in a non-endocytic mode, even at low micromolar concentration. We show that such thiol- or HaloTag-reactive additives can result in covalently anchored CPPs on the cell surface, which are highly effective at co-delivering protein cargoes. Taking advantage of the thiol reactivity of our most effective CPP additive, we show that Cys-containing proteins can be readily delivered into the cytosol by simple co-addition of a slight excess of this CPP. Furthermore, we demonstrate the application of our ‘CPP-additive technique’ in the delivery of functional enzymes, nanobodies and full-length immunoglobulin-G antibodies. This new cellular uptake protocol greatly simplifies both the accessibility and efficiency of protein and antibody delivery, with minimal chemical or genetic engineering.

DOI: 10.1038/s41557-021-00661-x

Source: https://www.nature.com/articles/s41557-021-00661-x