细胞穿透肽在蛋白质细胞内递送给治疗红细胞相关疾病中的潜在作用。

The potential role of cell penetrating peptides in the intracellular delivery of proteins for therapy of erythroid related disorders.

机构信息

Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, Thessaloniki GR54124 Macedonia, Greece.

出版信息

Pharmaceuticals (Basel). 2013 Jan 7;6(1):32-53. doi: 10.3390/ph6010032.

Abstract

The erythroid related disorders (ERDs) represent a large group of hematological diseases, which in most cases are attributed either to the deficiency or malfunction of biosynthetic enzymes or oxygen transport proteins. Current treatments for these disorders include histo-compatible erythrocyte transfusions or allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy delivered via suitable viral vectors or genetically modified HSCs have been under way. Protein Transduction Domain (PTD) technology has allowed the production and intracellular delivery of recombinant therapeutic proteins, bearing Cell Penetrating Peptides (CPPs), into a variety of mammalian cells. Remarkable progress in the field of protein transduction leads to the development of novel protein therapeutics (CPP-mediated PTs) for the treatment of monogenetic and/or metabolic disorders. The "concept" developed in this paper is the intracellular protein delivery made possible via the PTD technology as a novel therapeutic intervention for treatment of ERDs. This can be achieved via four stages including: (i) the production of genetically engineered human CPP-mediated PT of interest, since the corresponding native protein either is missing or is mutated in the erythroid progenitor cell (ErPCs) or mature erythrocytes of patients; (ii) isolation of target cells from the peripheral blood of the selected patients; (iii) ex vivo transduction of cells with the CPP-mediated PT of interest; and (iv) re-administration of the successfully transduced cells back into the same patients.

摘要

红细胞相关疾病(ERDs)代表了一大类血液疾病,这些疾病在大多数情况下归因于生物合成酶或氧气转运蛋白的缺乏或功能障碍。目前对这些疾病的治疗包括组织相容性红细胞输血或同种异体造血干细胞(HSC)移植。通过合适的病毒载体或基因修饰的 HSCs 进行的基因治疗已经在进行中。蛋白转导结构域(PTD)技术允许生产和将携带穿透肽(CPP)的重组治疗性蛋白递送至各种哺乳动物细胞内。蛋白转导领域的显著进展导致了新型蛋白治疗剂(CPP 介导的 PTs)的开发,用于治疗单基因和/或代谢疾病。本文提出的“概念”是通过 PTD 技术实现的细胞内蛋白递送来治疗 ERDs,这是一种新的治疗干预措施。这可以通过四个阶段来实现:(i)生产基因工程的人 CPP 介导的 PT,因为在红细胞前体细胞(ErPCs)或患者的成熟红细胞中相应的天然蛋白缺失或发生突变;(ii)从选定患者的外周血中分离靶细胞;(iii)用 CPP 介导的 PT 对细胞进行体外转导;和(iv)将成功转导的细胞重新给予同一患者。

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