Cardiac-Targeting Peptide: From Discovery to Applications.

Cardiac-Targeting Peptide: From Discovery to Applications.
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DOI:
10.3390/biom13121690
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发表时间:
2023-11-23
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
作者:

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尽管在预防、诊断和治疗方面取得了重大进展,但心血管疾病仍然是美国的头号死亡原因,在发展中国家,心血管疾病的发病率以惊人的速度攀升。靶向给药到心脏一直是一个崇高的目标,通过各种策略实现,从直接心脏内或心包内给药,冠状动脉内输注,以至腺病毒、慢病毒和腺相关病毒载体,这些载体对心脏组织具有偏好(如果不是完全的心脏选择性)。细胞穿透肽(CPP)是一种5-30个氨基酸的多肽,能够穿透细胞膜屏障,携带的货物大小是细胞膜的几倍,具有完整的功能。近30年前被发现,其中第一个CPP来自HIV外壳蛋白转录反式激活因子。虽然CPP是一种高效的CPP,但其强大的穿越任何细胞膜屏障的能力,包括穿越血脑屏障和非特异性转导神经元组织的能力,限制了其临床应用。有几种策略被用来识别细胞或组织特异性的CPP,其中之一是噬菌体展示。使用后一种技术,我们在十多年前就确定了一种心肌细胞靶向肽(CTP),这一发现已经得到世界各地的几个独立实验室的证实,这些实验室在临床前动物模型中将CTP用于无数不同的目的。本出版物的目的是对CTP的鉴定、验证和应用进行全面综述,并概述其在诊断和治疗应用中的潜力,特别是在靶向RNA干扰领域。
Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adenoviral, lentiviral, and adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell-penetrating peptides (CPP) are 5–30-amino-acid-long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood–brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell- or tissue-specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte-targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for a myriad of different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outline its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.
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