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针对前列腺特异性抗原的 2'F 修饰 RNA 适体的筛选及其在诊断和治疗中的评估。

Selection of 2'F-modified RNA aptamers against prostate-specific antigen and their evaluation for diagnostic and therapeutic applications.

机构信息

Nanobiotechnology and Bioanalysis group, Department of Chemical Engineering, Universitat Rovira i Virgili, 43007, Tarragona, Spain,

出版信息

Anal Bioanal Chem. 2013 Nov;405(28):9149-57. doi: 10.1007/s00216-013-7350-y. Epub 2013 Sep 17.

DOI:10.1007/s00216-013-7350-y
PMID:24043377
Abstract

Currently, prostate-specific antigen (PSA) is considered to be the most sensitive marker available for prostate cancer detection and for monitoring of disease progression. In addition to its importance as a tumor marker, PSA has a role in the biological activity of cancer growth and proliferation. Therefore, the inhibition or activation of its biological activity may be used in prostate cancer therapy. Here, we describe the isolation and characterization of new 2'F-modified RNA aptamers directed against PSA. Binding studies demonstrate the ability of these new aptamers to specifically recognize their target with dissociation constants in the nanomolar range. In order to demonstrate the functionality of the selected aptamers, an apta-PCR approach was used for the quantitative detection of PSA, achieving a limit of detection of 11 nM. Furthermore, the potential use of the selected aptamers in therapeutics was demonstrated with the 2'F-modified aptamers being highly stable in human serum and having the ability to moderate the activity of PSA, which will be explored for the treatment of prostate cancer.

摘要

目前,前列腺特异性抗原(PSA)被认为是用于前列腺癌检测和疾病进展监测的最敏感标志物。除了作为肿瘤标志物的重要性外,PSA 在癌症生长和增殖的生物学活性中也发挥作用。因此,其生物学活性的抑制或激活可能用于前列腺癌的治疗。在这里,我们描述了针对 PSA 的新型 2'F 修饰 RNA 适体的分离和鉴定。结合研究表明,这些新的适体能特异性地识别其靶标,解离常数在纳摩尔范围内。为了证明所选适体的功能,使用适体-PCR 方法对 PSA 进行定量检测,检测限达到 11 nM。此外,所选适体在治疗中的潜在用途也通过 2'F 修饰的适体在人血清中具有高度稳定性并能够调节 PSA 的活性来证明,这将用于治疗前列腺癌。

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