Protein based therapeutics with high specificities and low off-target effects are used for transient and accurate manipulation of cell functions. However, developing safe and efficient carriers for intracellular delivery of active therapeutic proteins is a long-standing challenge. Here we report a combinatorial library of chalcogen (O, S, Se) containing lipidoid nanoparticles (LNPs) as efficient nanocarriers for intracellular delivery of negatively supercharged Cre recombinase ((-30)GFP-Cre) and anionic Cas9:single-guide RNA (Cas9:sgRNA) ribonucleoprotein (RNP) for genome editing. The structure-activity relationship between the lipidoids and intracellular protein delivery efficiencies was explored and it was demonstrated that the newly developed LNPs are effective for gene recombination in vivo.

基于蛋白质的疗法具有高特异性和低脱靶效应，可用于瞬时且准确地操纵细胞功能。然而，开发安全有效的载体来细胞内递送活性治疗蛋白是一个长期存在的挑战。在这里，我们报告了一个包含类脂质纳米颗粒 (LNP) 的硫族元素 (O、S、Se) 组合文库，作为有效的纳米载体，用于细胞内递送负超电荷 Cre 重组酶 ((-30)GFP-Cre) 和阴离子 Cas9:单向导 RNA ( Cas9:sgRNA) 核糖核蛋白 (RNP) 用于基因组编辑。探索了类脂质与细胞内蛋白质递送效率之间的构效关系，并证明新开发的 LNP 对体内基因重组有效。