Abstract
The pathophysiology of sickle cell disease (SCD) is dependent on the polymerization of deoxygenated sickle hemoglobin (HbS), leading to erythrocyte deformation (sickling) and vaso-occlusion within the microvasculature. Following deoxygenation, there is a delay time before polymerization is initiated, during which nucleation of HbS monomers occurs. An agent with the ability to extend this delay time or slow polymerization would therefore hold a therapeutic, possibly curative, potential. We used the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method to screen for HbS-binding RNA aptamers modified with nuclease-resistant 2′-fluoropyrimidines. Polymerization assays were employed to identify aptamers with polymerization-inhibitory properties. Two noncompeting aptamers, DE3A and OX3B, were found to bind hemoglobin, significantly increase the delay time, and reduce the rate of polymerization of HbS. These modifiable, nuclease-resistant aptamers are potential new therapeutic agents for SCD.
Original language | English (US) |
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Pages (from-to) | 354-364 |
Number of pages | 11 |
Journal | Nucleic Acid Therapeutics |
Volume | 27 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2017 |
Keywords
- Aptamer
- RNA
- hemoglobin
- polymerization
- sickle cell disease
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Genetics
- Drug Discovery