含硫脂脂质体组合文库用于基因编辑蛋白的细胞内递送。
Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteins.
机构信息
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610065, PR China.
出版信息
Biomaterials. 2018 Sep;178:652-662. doi: 10.1016/j.biomaterials.2018.03.011. Epub 2018 Mar 8.
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.
具有高特异性和低脱靶效应的蛋白质治疗药物可用于瞬时和精确地操纵细胞功能。然而，开发用于细胞内递呈活性治疗蛋白的安全有效的载体是一个长期存在的挑战。在这里，我们报告了一个包含硫属（氧、硫、硒）的脂质体纳米颗粒（LNPs）的组合文库，作为用于细胞内递呈带负电荷的 GFP-Cre 重组酶（(-30)GFP-Cre）和阴离子 Cas9:单指导 RNA（Cas9:sgRNA）核糖核蛋白（RNP）的有效纳米载体，用于基因组编辑。我们探索了脂质体与细胞内蛋白递呈效率之间的构效关系，并证明了新开发的 LNPs 可有效地在体内进行基因重组。
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