期刊
METHODS
卷 103, 期 -, 页码 175-179出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymeth.2016.03.004
关键词
RNA aptamers; RNA secondary and tertiary structure; Structural algorithms; Vfold2D model; Vfold3D model; Prostate specific membrane antigen (PSMA); A9 aptamer; A9g aptamer; NAALADase Assay
资金
- NCI NIH HHS [R01 CA138503] Funding Source: Medline
- NHLBI NIH HHS [T32 HL007344] Funding Source: Medline
- NIDCR NIH HHS [R21 DE019953] Funding Source: Medline
- NIGMS NIH HHS [R01 GM063732] Funding Source: Medline
RNA aptamers represent an emerging class of biologics that can be easily adapted for personalized and precision medicine. Several therapeutic aptamers with desirable binding and functional properties have been developed and evaluated in preclinical studies over the past 25 years. However, for the majority of these aptamers, their clinical potential has yet to be realized. A significant hurdle to the clinical adoption of this novel class of biologicals is the limited information on their secondary and tertiary structure. Knowledge of the RNA's structure would greatly facilitate and expedite the post-selection optimization steps required for translation, including truncation (to reduce costs of manufacturing), chemical modification (to enhance stability and improve safety) and chemical conjugation (to improve drug properties for combinatorial therapy). Here we describe a structural computational modeling methodology that when coupled to a standard functional assay, can be used to determine key sequence and structural motifs of an RNA aptamer. We applied this methodology to enable the truncation of an aptamer to prostate specific membrane antigen (PSMA) with great potential for targeted therapy that had failed previous truncation attempts. This methodology can be easily applied to optimize other aptamers with therapeutic potential. (C) 2016 Published by Elsevier Inc.
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