In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system.
In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system.
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DOI：
10.1126/sciadv.abo2954
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发表时间：
2022-09-30
期刊：
影响因子：
13.6
通讯作者：
Pellois, Jean-Philippe
中科院分区：
文献类型：
--
作者：
Allen, Jason K.;Sutherland, Theresa C.;Prater, Austin R.;Geoffroy, Cedric G.;Pellois, Jean-Philippe
我们报道了Cre重组酶通过与HIV-TAT衍生肽的简单共注射在小鼠体内神经细胞中的成功传递。Cre递送激活皮层神经元和星形胶质细胞中报告基因的表达，而不会造成组织损伤，其转导效率与常用的腺相关病毒相当或超过。我们的数据表明，递送肽介导有效内吞Cre的细胞内体渗漏和胞质逃逸。因此，肽以反式作用，不需要与有效载荷偶联，大大简化了样品制备。此外，递送肽完全由天然氨基酸组成，因此很容易被细胞降解和加工。我们设想这种方法将有利于需要将蛋白质瞬间引入体内细胞的应用。促进内体快速逃逸的肽在小鼠脑组织中实现细胞内蛋白质递送。
We report on the successful delivery of the Cre recombinase enzyme in the neural cells of mice in vivo by simple coinjection with peptides derived from HIV-TAT. Cre delivery activates the expression of a reporter gene in both neurons and astrocytes of the cortex without tissue damage and with a transduction efficiency that parallels or exceeds that of a commonly used adeno-associated virus. Our data indicate that the delivery peptides mediate efficient endosomal leakage and cytosolic escape in cells that have endocytosed Cre. The peptides, therefore, act in trans and do not require conjugation to the payload, greatly simplifying sample preparation. Moreover, the delivery peptides are exclusively composed of natural amino acids and are consequently readily degradable and processed by cells. We envision that this approach will be beneficial to applications that require the transient introduction of proteins into cells in vivo. Peptides that promote rapid endosomal escape achieve intracellular protein delivery in mouse brain tissue.
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影响因子：
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作者：
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通讯作者：
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Kondow-McConaghy HM;Muthukrishnan N;Erazo-Oliveras A;Najjar K;Juliano RL;Pellois JP
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