Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells
Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells
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DOI：
10.1002/anie.201904894
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发表时间：
2019-09-18
影响因子：
16.6
通讯作者：
Gianneschi, Nathan C.
中科院分区：
文献类型：
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作者：
Blum, Angela P.;Nelles, David A.;Gianneschi, Nathan C.
缺乏向活细胞运送功能蛋白质的有效手段是生物技术和医学中的一个中心问题。在这里，我们报告了通过高密度细胞穿透性多肽刷状聚合物将一种活性的DNA修饰酶高效地输送到人类干细胞。Cre重组酶与荧光团标记的聚合物载体混合，然后直接应用于诱导的多能干细胞或HEK293T细胞。这导致了Cre蛋白的有效传递，通过激活基因组整合的Cre介导的重组报告来衡量。我们观察到，使用细胞穿透肽的刷状聚合物制剂促进了Cre的传递，但单独使用寡肽或显示在纳米颗粒上的寡肽并不能。总体而言，我们报告了将基因组修饰酶有效地传递到干细胞，这种酶可能适用于其他难以转导的细胞类型。
The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide brush polymers. Cre recombinase is mixed with a fluorophore-tagged polymer carrier and then applied directly to induced pluripotent stem cells or HEK293T cells. This results in efficient delivery of Cre protein as measured by activation of a genomically integrated Cre-mediated recombination reporter. We observed that brush polymer formulations utilizing cell penetrating peptides promoted Cre delivery but oligopeptides alone or oligopeptides displayed on nanoparticles did not. Overall, we report the efficient delivery of a genome-modifying enzyme to stem cells that may be generalizable to other, difficult-to-transduce cell types.