Philippou Styliana, Mastroyiannopoulos Nikolaos P, Tomazou Marios, Oulas Anastasios, Ackers-Johnson Matthew, Foo Roger S, Spyrou George M, Phylactou Leonidas A
Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.
Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.
Pharmaceuticals (Basel). 2023 Sep 6;16(9):1264. doi: 10.3390/ph16091264.
In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers that recognize specific cell types within a tissue. Such aptamers could potentially improve the development of drugs for several diseases, including neuromuscular disorders, by targeting solely the proteins involved in their pathogenesis. Here, we describe our attempt to utilize in vivo SELEX with a modification in the methodology that drives the selection of intravenously injected aptamers towards a specific cell type of interest. Our data suggest that the incorporation of a cell enrichment step can direct the in vivo localization of RNA aptamers into cardiomyocytes, the cardiac muscle cells, more readily over other cardiac cells. Given the crucial role of cardiomyocytes in the disease pathology in DMD cardiomyopathy and therapy, these aptamers hold great potential as drug delivery vehicles with cardiomyocyte selectivity.
体内指数富集配体系统进化技术（In vivo SELEX）是指数富集配体系统进化技术（SELEX）的一种先进变体，它能够开发出能够在其天然微环境中直接识别靶标的适配体。虽然这种方法确保了所选适配体具有更高的转化潜力，但它并不能筛选出能够识别组织内特定细胞类型的适配体。这类适配体有可能通过仅靶向参与多种疾病（包括神经肌肉疾病）发病机制的蛋白质，来促进针对这些疾病的药物研发。在此，我们描述了我们尝试利用体内指数富集配体系统进化技术，并对方法进行修改，以驱使对静脉注射的适配体进行筛选，使其朝向特定的目标细胞类型。我们的数据表明，加入细胞富集步骤可以使RNA适配体在体内更易于定位到心肌细胞（即心脏肌肉细胞），而不是其他心脏细胞。鉴于心肌细胞在杜氏肌营养不良症心肌病的疾病病理和治疗中起着关键作用，这些适配体作为具有心肌细胞选择性的药物递送载体具有巨大潜力。
