Development of mRNA ablation using completely new functional nucleic acid constructs

真基因沉默是一种利用tRNase ZL和小向导RNA（sgRNA）切割由细胞靶RNA组成的前tRNA样或微前tRNA样复合物来删除特定细胞RNA的新方法。我们研究了七聚体型sgRNA可用作治疗血液恶性肿瘤的核酸药物的可能性。我们研究了人工sgRNA对影响白血病细胞的靶向sgRNA的mRNA的影响。我们证实了sgRNA可以在没有任何转染试剂的情况下被细胞摄取，并且靶向几种肿瘤相关mRNA的裸sgRNA可以降低几种白血病细胞系中特定mRNA水平和肿瘤相关蛋白的量。这些sgRNA有效地诱导了这些细胞的凋亡。这些令人鼓舞的发现使我们关注靶向抗凋亡mRNAs的七聚体型sgRNA可用作抗血液恶性肿瘤的RNA药物的可能性。

TRUE gene silencing is a new method to delete specific cellular RNAs by using tRNase ZL and small guide RNA (sgRNA) that cleaves a pre-tRNA-like or micro-pre-tRNA-like complex consisting of cellular target RNA. We investigated the possibility that heptamer-type sgRNA can be used as nucleic acid medicine to treat hematological malignancies. We investigated the effect of artificial sgRNAs on mRNAs which -targeting sgRNAs affect leukemic cells. We confirmed that sgRNA can be taken up by cells without any transfection reagents, and that the naked sgRNAs targeting several tumor-associated mRNA can reduce specific mRNA levels and the amounts of tumor-associated protein in several leukemic cell lines. These sgRNAs efficiently induced apoptosis in these cells.These encouraging findings lead us to follow the possibility that heptamer-type sgRNAs targeting anti-apoptotic mRNAs can be used as RNA medicine against hematological malignancies.