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Composition for designing and developing universal anticancer drugs and vaccines

机译:用于设计和开发通用抗癌药物和疫苗的组合物

摘要

Disclosed are a design and method for developing novel anti-tumor/cancer drugs, vaccines and therapies, using microRNA (miRNA) and its shRNA homologues/derivatives. More particularly, disclosed are the use of a nucleic acid composition capable of expressing mir-302-like gene silencing effectors upon delivery into human cells and then silencing mir-302-targeted cell cycle regulators and oncogenes, resulting in an inhibitory effect on tumor/cancer cell growth and metastasis. Mir-302 is the most predominant miRNA found in human embryonic stem (hES) and induced pluripotent stem (iPS) cells, yet its function is unclear. The present invention establishes that in humans mir-302 concurrently suppressed both cyclin-E-CDK2 and cyclin-D-CDK4/6 pathways and eventually blocked over 70% of the G1-S transition. Simultaneously, mir-302 also silences BMI-1, a cancer stem cell marker, and subsequently promotes the tumor suppressor functions of p16Ink4a and p14/p19Arf in inhibiting CDK4/6-mediated cell proliferation.
机译:公开了使用微RNA(miRNA)及其shRNA同源物/衍生物开发新的抗肿瘤/癌症药物,疫苗和疗法的设计和方法。更具体地,公开了一种核酸组合物的用途,该核酸组合物能够在递送到人细胞中时表达mir-302样基因沉默效应子,然后沉默mir-302靶向的细胞周期调节剂和致癌基因,从而对肿瘤/癌细胞的生长和转移。 Mir-302是在人类胚胎干(hES)和诱导性多能干(iPS)细胞中发现的最主要的miRNA,但其功能尚不清楚。本发明建立了在人类中mir-302同时抑制细胞周期蛋白-E-CDK2和细胞周期蛋白-D-CDK4 / 6途径,并最终阻断了超过70%的G1-S转变。同时,mir-302还沉默了癌症干细胞标记物BMI-1,并随后增强了p16Ink4a和p14 / p19Arf的肿瘤抑制功能,以抑制CDK4 / 6介导的细胞增殖。

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