评估双七聚体 sgRNA 作为一种治疗多发性骨髓瘤的潜在治疗药物。
Evaluation of double heptamer-type sgRNA as a potential therapeutic agent against multiple myeloma.
机构信息
Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Higashijima 265-1, Akihaku, Niigata, Niigata 956-8603, Japan.
Department of Orthoptist Training, Niigata College of Medical Technology, Kamishineicho 5-13-3, Nishiku, Niigata, Niigata 950-2076, Japan.
出版信息
Blood Cells Mol Dis. 2019 Nov;79:102341. doi: 10.1016/j.bcmd.2019.102341. Epub 2019 Jun 12.
Emergence of drug-resistant mutations in the course of myeloma cell evolution and subsequent relapse of myeloma appears to be currently inevitable in most patients. To remedy this situation, we are trying to develop therapeutic small guide RNAs (sgRNAs) based on tRNase Z-utilizing efficacious gene silencing (TRUE gene silencing), an RNA-mediated gene expression control technology. We designed two sets of double heptamer-type sgRNA, which target the human BCL2 mRNA. Both sets of double heptamer-type sgRNA reduced viability of human myeloma cell lines, RPMI-8226 and KMM-1. We also performed a mouse xenograft experiment to examine how the double heptamer-type sgRNA DHa1(BCL2)/DHa2(BCL2) can reduce the growth of KMM-1 cells in vivo. Median survival periods of the sgRNA cohorts were greater than that of the control cohort by 11-43 days. Furthermore, we designed two sets of double heptamer-type sgRNA, which target the human CCND1 mRNA, and both sets synergistically reduced RPMI-8226 cell viability.
在骨髓瘤细胞进化过程中出现耐药突变以及随后骨髓瘤的复发，在大多数患者中似乎是不可避免的。为了弥补这种情况，我们正试图开发基于 tRNase Z 利用有效的基因沉默（TRUE 基因沉默）的治疗性小向导 RNA（sgRNA），这是一种 RNA 介导的基因表达控制技术。我们设计了两组靶向人 BCL2 mRNA 的双链七聚体 sgRNA。两组双链七聚体 sgRNA 均降低了人骨髓瘤细胞系 RPMI-8226 和 KMM-1 的活力。我们还进行了小鼠异种移植实验，以研究双链七聚体 sgRNA DHa1(BCL2)/DHa2(BCL2)如何在体内减少 KMM-1 细胞的生长。sgRNA 组的中位生存期比对照组长 11-43 天。此外，我们设计了两组靶向人 CCND1 mRNA 的双链七聚体 sgRNA，两组均协同降低 RPMI-8226 细胞活力。
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