用以標的凝血因子XIII的適體及其用途

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

108143991

專利證號

I 739226

專利獲證名稱

用以標的凝血因子XIII的適體及其用途

專利所屬機關 (申請機關)

長庚大學

獲證日期

2021/09/11

技術說明

在急性期治療缺血性心臟疾病及中風時，目前的策略是給予組織胞漿素原活化劑，但常會導致病患出血的系統性副作用，而標靶性給藥方式應有助於減少其副作用。由於第十三凝血因子(FXIII)參與凝血反應並可穩定血栓，亦會表現在活化之血小板表面參與血栓形成，極有潛力成為給藥標的。過去文獻已報導開發專一性結合於FXIII之抗體或短胜肽，但礙於胺基酸對於溫度及酸鹼的敏感，以及昂貴的合成成本，未見進一步應用。核酸組成的適體(aptamer)具有分子穩定及製作成本低廉的特性，經由本實驗室篩選出專一性結合於FXIII aptamer系列，可以利用FXIII aptamer的高親和力辨認FXIII產生標靶效應、並提供一定量FXIII的平台。例如將該aptamer修飾生物素，可以經由與鏈親和素鍵結山葵過氧化酶，在免疫斑點試驗中辨認到FXIII的訊號；將aptamer修飾羧基螢光素，可以在流式細胞儀中區分活化及為活化之血小板；也能在血漿的免疫螢光組織染色中，辨認纖維蛋白和活化之血小板，也可應用於引導藥物至血栓處作用。 In the acute treatment of ischemic heart disease and stroke, the current strategy is administration of tissue plasminogen activator that may cause hemorrhagic side effects. Targeted delivery of the drug is a potential resolution. Coagulation factor XIII (FXIII) participates in coagulation cascade by increasing thrombus stability, which is also expressed on the surface of activated, but not resting platelets. It has been demonstrated that antibodies or short peptide have been developed that specifically bind to FXIII. However, probably due to low stability and high cost in production, the application is limited. Alternatively, aptamers composed of nucleic acids are relatively stable and low in cost of production. Through screening of aptamers that specifically bind to FXIII, selected aptamers may be used alternatively to antibodies or short peptides. For example, through conjugation the streptavidin-horseradish peroxidase, the biotin-labeled aptamers can be used to detect the FXIII by dot blot; the fluorescence-labeled aptamers can be used to classify the activated/non-activated platelets by flow cytometry and detect the fibrin by immunofluorescence. The targeting aptamers may be applied to guide drugs to thrombus in the blood vessels.

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