Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.
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DOI:
10.34133/bmef.0035
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发表时间:
2024
期刊:
影响因子:
--
通讯作者:
Tsourkas A
Tsourkas A
中科院分区:
其他
文献类型:
--
作者:
Chan A;Tsourkas A

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蛋白质生物制剂是具有多种抑制和酶功能的强大治疗剂。然而,由于它们不能穿过质膜,它们的临床应用仅限于细胞外应用。克服这一生理障碍将释放蛋白质药物治疗许多疑难杂症的潜力。在这篇综述中,我们强调了实现重组蛋白质的胞质递送所取得的进展。我们首先考虑细胞内蛋白质递送作为一种药物模式相比,现有的食品和药物管理局批准的药物模式。然后,我们总结了已报道的实现蛋白质内化的策略。这些技术可以大致分为3类:物理方法,直接蛋白质工程和纳米载体介导的递送。最后,我们强调现有的挑战,胞质蛋白质输送,并提供了未来的发展前景。
Protein biologics are powerful therapeutic agents with diverse inhibitory and enzymatic functions. However, their clinical use has been limited to extracellular applications due to their inability to cross plasma membranes. Overcoming this physiological barrier would unlock the potential of protein drugs for the treatment of many intractable diseases. In this review, we highlight progress made toward achieving cytosolic delivery of recombinant proteins. We start by first considering intracellular protein delivery as a drug modality compared to existing Food and Drug Administration-approved drug modalities. Then, we summarize strategies that have been reported to achieve protein internalization. These techniques can be broadly classified into 3 categories: physical methods, direct protein engineering, and nanocarrier-mediated delivery. Finally, we highlight existing challenges for cytosolic protein delivery and offer an outlook for future advances.
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