期刊
NUCLEIC ACID THERAPEUTICS
卷 21, 期 5, 页码 299-314出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/nat.2011.0313
关键词
-
资金
- National Institutes of Health [1RO1 CA138503-01, 1R21DE019953-01, GM063732, R21GM088517]
- National Science Foundation [MCB0920411, MCB0920067, DBI-0953839]
- Roy J. Carver Charitable Trust [RJCCT 01-224]
- RSNA [RR0905]
RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and- error process, which is time consuming and inefficient. Here, we used a rational truncation'' approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA), with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据