Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem.
Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem.
复制标题
DOI：
10.1515/bmc-2017-0023
复制
发表时间：
2017-09-26
影响因子：
--
通讯作者：
McMurry JL
中科院分区：
文献类型：
--
作者：
LeCher JC;Nowak SJ;McMurry JL
细胞穿透肽（CPP）长期以来一直在为治疗和研究目的操纵活细胞方面具有很大的前景。它们允许从大的寡聚蛋白质到核酸和小分子的各种生物分子快速有效地穿过细胞质膜。除了少数例外，如果一种分子可以与CPP结合，它就可以被递送到细胞中。然而，在该领域中越来越多的认识是CPP-货物融合物大部分保持被捕获在内体中，并且最终被靶向降解或再循环，而不是释放到细胞质中或运输到期望的亚细胞目的地。这种“内体逃逸问题”混淆了努力开发CPP为基础的药物，酶，质粒等交付方法的概念概述提供了一个简短的历史CPP研究和讨论当前的问题，在该领域的主要重点内体逃逸问题，其中几个有前途的潜在解决方案已经开发。我们是否正在开发技术来提供治疗方法，如siRNA，CRISPR/Cas复合物和其他目前由于无法进入细胞而失败的技术，或者我们只是在追逐另一种有前途但不可行的技术？我们提出了乐观的理由。
Cell-penetrating peptides (CPPs) have long held great promise for the manipulation of living cells for therapeutic and research purposes. They allow a wide array of biomolecules from large, oligomeric proteins to nucleic acids and small molecules to rapidly and efficiently traverse cytoplasmic membranes. With few exceptions, if a molecule can be associated with a CPP, it can be delivered into a cell. However, a growing realization in the field is that CPP-cargo fusions largely remain trapped in endosomes and are eventually targeted for degradation or recycling rather than released into the cytoplasm or trafficked to a desired subcellular destination. This ‘endosomal escape problem’ has confounded efforts to develop CPP-based delivery methods for drugs, enzymes, plasmids, etc. This conceptual overview provides a brief history of CPP research and discusses current issues in the field with a primary focus on the endosomal escape problem, of which several promising potential solutions have been developed. Are we on the verge of developing technologies to deliver therapeutics such as siRNA, CRISPR/Cas complexes and others that are currently failing because of an inability to get into cells, or are we just chasing after another promising but unworkable technology? We make the case for optimism.