Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, USA.
Centro Universitario Contra el Cáncer (CUCC), Servicio de Oncología, Universidad Autónoma de Nuevo León, Hospital Universitario "Dr. José Eleuterio González", Nuevo, León 64460, Mexico.
Molecules. 2021 Oct 28;26(21):6525. doi: 10.3390/molecules26216525.
The application of aptamers in biomedicine is emerging as an essential technology in the field of cancer research. As small single-stranded DNA or RNA ligands with high specificity and low immunogenicity for their targets, aptamers provide many advantages in cancer therapeutics over protein-based molecules, such as antibodies. Vimentin is an intermediate filament protein that is overexpressed in endothelial cells of cancerous tissue. High expression levels of vimentin have been associated with increased capacity for migration and invasion of the tumor cells. We have selected and identified thioated aptamers with high specificity for vimentin using human ovarian cancer tissues. Tentative binding motifs were chosen for two vimentin aptamers based on predicted secondary structures. Each of these shorter, tentative binding motifs was synthesized, purified, and characterized via cell binding assays. Two vimentin binding motifs with high fidelity binding were selected and further characterized via cell and tissue binding assays, as well as flow cytometric analysis. The equilibrium binding constants of these small thioated aptamer constructs were also determined. Future applications for the vimentin binding aptamer motifs include conjugation of the aptamers to synthetic dyes for use in targeted imaging and therapy, and ultimately more detailed and precise monitoring of treatment response and tumor progression in ovarian pathology.
适体在生物医学中的应用作为癌症研究领域的一项重要技术正在兴起。作为针对其靶标的高特异性和低免疫原性的小单链 DNA 或 RNA 配体，适体在癌症治疗方面比基于蛋白质的分子（如抗体）具有许多优势。波形蛋白是一种中间丝蛋白，在癌组织的内皮细胞中过度表达。高表达的波形蛋白与肿瘤细胞迁移和侵袭能力的增加有关。我们使用人卵巢癌组织选择并鉴定了针对波形蛋白的高特异性硫代适体。基于预测的二级结构，为两个波形蛋白适体选择了暂定的结合基序。每个这些较短的暂定结合基序都通过细胞结合测定法进行合成、纯化和表征。选择了具有高保真结合的两个波形蛋白结合基序，并通过细胞和组织结合测定法以及流式细胞术分析进一步进行了表征。这些小的硫代适体构建体的平衡结合常数也被确定。波形蛋白结合适体基序的未来应用包括将适体与合成染料缀合，用于靶向成像和治疗，以及最终更详细和精确地监测卵巢病理学中的治疗反应和肿瘤进展。
