Genetic and Covalent Protein Modification Strategies to Facilitate Intracellular Delivery.
Genetic and Covalent Protein Modification Strategies to Facilitate Intracellular Delivery.
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DOI：
10.1021/acs.biomac.1c00745
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发表时间：
2021-12-13
影响因子：
6.2
通讯作者：
Obermeyer, Allie C.
中科院分区：
文献类型：
--
作者：
Horn, Justin M.;Obermeyer, Allie C.
基于蛋白质的疗法代表了已批准的疾病治疗中快速增长的部分。蛋白质的成功细胞内递送是扩大蛋白质治疗的体内和体外应用的重要前提。直接修饰蛋白质和肽以改善胞质易位是提高递送效率和扩大细胞内蛋白质治疗的可行性的有前途的方法。在这篇综述中，我们介绍了细胞内递送的合成和遗传蛋白质修饰的最新进展。讨论了基于主动内吞作用和被动内化途径，然后回顾了改进胞质递送的修饰方法。在确定如何修饰蛋白质后，涵盖了促进细胞内递送的一般策略，例如化学增压或包含细胞穿透基序。然后我们概述了促进内体逃逸的蛋白质修饰。我们最终检查了两类潜在的治疗蛋白、抗体和相关抗体片段以及基因编辑蛋白（例如 cas9）的传递。
Protein-based therapeutics represent a rapidly growing segment of approved disease treatments. Successful intracellular delivery of proteins is an important precondition for expanded in vivo and in vitro applications of protein therapeutics. Direct modification of proteins and peptides for improved cytosolic translocation are a promising method of increasing delivery efficiency and expanding the viability of intracellular protein therapeutics. In this review, we present recent advances in both synthetic and genetic protein modifications for intracellular delivery. Active endocytosis-based and passive internalization pathways are discussed, followed by a review of modification methods for improved cytosolic delivery. After establishing how proteins can be modified, general strategies for facilitating intracellular delivery, such as chemical supercharging or inclusion of cell-penetrating motifs, are covered. We then outline protein modifications that promote endosomal escape. We finally examine delivery of two potential classes of therapeutic proteins, antibodies and associated antibody fragments, and gene editing proteins, such as cas9.
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DOI：
10.1073/pnas.93.22.12531
发表时间：
1996-10-29
影响因子：
11.1
作者：
Ballard, JD;Collier, RJ;Starnbach, MN
通讯作者：
Starnbach, MN
影响因子：
15
作者：
Alsaiari, Shahad K.;Patil, Sachin;Khashab, Niveen M.
通讯作者：
Khashab, Niveen M.
影响因子：
14
作者：
Akita, Hidetaka;Kudo, Asako;Harashima, Hideyoshi
通讯作者：
Harashima, Hideyoshi
影响因子：
8.4
作者：
Bisseret P;Abdelkafi H;Blanchard N
通讯作者：
Blanchard N
影响因子：
64.8
作者：
Abudayyeh OO;Gootenberg JS;Essletzbichler P;Han S;Joung J;Belanto JJ;Verdine V;Cox DBT;Kellner MJ;Regev A;Lander ES;Voytas DF;Ting AY;Zhang F
通讯作者：
Zhang F