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RNA aptamer therapy for vaso-occlusion in sickle cell disease.

Publication ,  Journal Article
Burnette, AD; Nimjee, SM; Batchvarova, M; Zennadi, R; Telen, MJ; Nishimura, J-I; Sullenger, BA
Published in: Nucleic Acid Ther
August 2011

Patients with sickle cell disease (SCD) often suffer painful vaso-occlusive episodes caused in part by the adhesion of sickle erythrocytes (SS-RBC) to the vascular endothelium. To investigate inhibition of SS-RBC adhesion as a possible treatment for vaso-occlusion, 2 adhesion molecules, α(v)β(3) and P-selectin, were targeted by high-affinity RNA aptamers. An in vitro flow chamber assay was used to test the antiadhesion activity of α(v)β(3) aptamer clone 17.16. Human SS-RBC were passed across a confluent monolayer of thrombin-stimulated human umbilical vein endothelial cells (HUVEC) at a constant rate. α(v)β(3) aptamer reduced SS-RBC adhesion to activated endothelial cells to the level seen with untreated HUVEC. An aptamer reactive with complement component 8 was used as a negative control and exerted no inhibition, confirming the specificity of α(v)β(3) aptamer (P=0.04). At 2 dyn/cm(2) shear stress, 30 nM α(v)β(3) aptamer showed maximal effect in decreasing SS-RBC adhesion to HUVEC. The antiadhesive activity of the P-selectin aptamer clone PF377 was also tested using HUVEC pretreated with IL-13 to upregulate expression of P-selectin as seen in activated endothelial cells. At 1 dyn/cm(2) shear stress, 60 nM of P-selectin aptamer had antiadhesion activity similar to heparin, a known inhibitor of SS-RBC adhesion to P-selectin. A negative control did not prevent adhesion (P=0.05). These data show the potential utility of aptamers to block endothelial adhesion molecules to prevent or treat vaso-occlusion in SCD.

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Published In

Nucleic Acid Ther

DOI

EISSN

2159-3345

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

275 / 283

Location

United States

Related Subject Headings

  • Pharmacology & Pharmacy
  • P-Selectin
  • Integrin alphaVbeta3
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • Erythrocytes
  • Cells, Cultured
  • Cell Adhesion
  • Biochemistry & Molecular Biology
  • Aptamers, Nucleotide
 

Citation

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Burnette, A. D., Nimjee, S. M., Batchvarova, M., Zennadi, R., Telen, M. J., Nishimura, J.-I., & Sullenger, B. A. (2011). RNA aptamer therapy for vaso-occlusion in sickle cell disease. Nucleic Acid Ther, 21(4), 275–283. https://doi.org/10.1089/nat.2010.0270
Burnette, Angela D., Shahid M. Nimjee, Milena Batchvarova, Rahima Zennadi, Marilyn J. Telen, Jun-Ichi Nishimura, and Bruce A. Sullenger. “RNA aptamer therapy for vaso-occlusion in sickle cell disease.Nucleic Acid Ther 21, no. 4 (August 2011): 275–83. https://doi.org/10.1089/nat.2010.0270.
Burnette AD, Nimjee SM, Batchvarova M, Zennadi R, Telen MJ, Nishimura J-I, et al. RNA aptamer therapy for vaso-occlusion in sickle cell disease. Nucleic Acid Ther. 2011 Aug;21(4):275–83.
Burnette, Angela D., et al. “RNA aptamer therapy for vaso-occlusion in sickle cell disease.Nucleic Acid Ther, vol. 21, no. 4, Aug. 2011, pp. 275–83. Pubmed, doi:10.1089/nat.2010.0270.
Burnette AD, Nimjee SM, Batchvarova M, Zennadi R, Telen MJ, Nishimura J-I, Sullenger BA. RNA aptamer therapy for vaso-occlusion in sickle cell disease. Nucleic Acid Ther. 2011 Aug;21(4):275–283.
Journal cover image

Published In

Nucleic Acid Ther

DOI

EISSN

2159-3345

Publication Date

August 2011

Volume

21

Issue

4

Start / End Page

275 / 283

Location

United States

Related Subject Headings

  • Pharmacology & Pharmacy
  • P-Selectin
  • Integrin alphaVbeta3
  • Humans
  • Human Umbilical Vein Endothelial Cells
  • Erythrocytes
  • Cells, Cultured
  • Cell Adhesion
  • Biochemistry & Molecular Biology
  • Aptamers, Nucleotide