Identification of Aptamers That Bind to Sickle Hemoglobin and Inhibit Its Polymerization

Shirley H. Purvis, Jeffrey R. Keefer, Yolanda M. Fortenberry, Emily A. Barron-Casella, James F. Casella

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)354-364
Number of pages11
JournalNucleic Acid Therapeutics
Volume27
Issue number6
DOIs
StatePublished - Dec 2017

Keywords

  • Aptamer
  • RNA
  • hemoglobin
  • polymerization
  • sickle cell disease

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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