适配体在免疫性疾病靶向治疗中的应用

Application of aptamers in the targeted treatment of immunological diseases

细胞因子是由活化的免疫细胞或非免疫细胞合成并分泌的小分子蛋白质,其主要通过与特定受体结合并激活相应下游信号转导通路,在免疫调控以及免疫性疾病的发生、发展过程中发挥广泛的生物学作用。迄今为止,基于抗体的细胞因子和(或)细胞因子受体的靶向阻断在免疫性疾病的治疗中已取得令人鼓舞的效果,但其高昂的治疗费用给患者带来极大的经济负担。适配体又称化学抗体,是体外合成并经人工筛选获得的、能与诸多靶标分子特异并高亲和结合的寡核苷酸片段。与抗体相比,适配体有着成本低廉、低免疫原性和易于修饰等诸多优势。因此,功能化适配体在免疫性疾病靶向治疗中的潜在应用前景吸引了越来越多研究者的关注。文章综述了在免疫调控中发挥重要作用的8种细胞因子[IL-1α、IL-6、IL-17、TNF-α、转化生长因子-β、IFN-γ、单核细胞趋化蛋白-1(MCP-1)和IFN-α诱导蛋白10]相关的特异性适配体的化学修饰及其在免疫和免疫相关性疾病治疗中应用的研究进展,并就未来适配体药物在临床特定免疫性疾病的精准靶向治疗中的潜在应用进行展望。

Cytokines are small molecular proteins released by activated immune cells or non-immune cells.Cytokines can play a wide range of biological roles in immune regulation and the incidence and progression of immune diseases by selectively binding with specific signals and activating the downstream immune signal transduction pathway.Encouraging efficacy has been achieved in the application of antibody-based cytokines or cytokine receptor monoclonal antibodies in the treatment of related immune diseases.Nevertheless,the high cost of administration based on monoclonal antibodies makes it unaffordable for patients.Aptamers,also known as chemical antibodies,are oligonucleotide fragments synthesized in vitro and obtained by artificial screening,which can specifically bind to multiple target molecules with high affinity.Compared with antibodies,aptamers have the advantages of low cost,low immunogenicity and convenient modification.Hence,the potential application prospect of functionalized aptamers in targeted therapy of immune diseases has attracted more and more attention from researchers.In this article,chemical modification of specific aptamers related to 8 types of cytokine aptamers(IL-1α,IL-6,IL-17,TNF-α,TGF-β,IFN-γ,MCP-1 and IP-10)which play critical roles in immune regulation was reviewed,the research progress in their application in the treatment for immune and immune-related diseases was summarized,and the potential application of aptamer drugs in precise targeted therapy for specific immune diseases was briefly predicted.