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A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.

Publication ,  Journal Article
White, RR; Roy, JA; Viles, KD; Sullenger, BA; Kontos, CD
Published in: Angiogenesis
2008

Tie2 is a receptor tyrosine kinase that is expressed predominantly in the endothelium and plays key roles in both physiological and pathological angiogenesis. The ligands for Tie2, the angiopoietins (Ang), perform opposing functions in vascular maintenance and angiogenesis; Ang1 regulates vascular quiescence, while Ang2 is thought to promote vascular destabilization and facilitate angiogenesis. However, the mechanisms responsible for these differences are not understood. To begin to elucidate the molecular differences between the angiopoietins, we previously developed a specific RNA aptamer inhibitor of Ang2. Here, we used the same iterative in vitro selection process, termed SELEX (Systematic Evolution of Ligands by EXponential enrichment), to screen a library of 2'-fluoro-modified ribonucleotides for Ang1-binding aptamers. After nine rounds of selection, we identified a single clone, ANG9-4, that bound with high affinity to human Ang1 (K ( d ) 2.8 nM) but not Ang2 (K ( d ) > 1 microM), demonstrating specificity for Ang1. ANG9-4 blocked Ang1-mediated Tie2 phosphorylation and downstream Akt activation. Moreover, ANG9-4 inhibited Ang1-induced endothelial cell survival. Together, these findings demonstrate the feasibility of developing an Ang1-inhibitory aptamer. ANG9-4 and its derivatives may provide useful tools for elucidating the biology of Ang1 and for treating certain angiogenic diseases.

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Published In

Angiogenesis

DOI

EISSN

1573-7209

Publication Date

2008

Volume

11

Issue

4

Start / End Page

395 / 401

Location

Germany

Related Subject Headings

  • Umbilical Veins
  • Signal Transduction
  • Receptor, TIE-2
  • Proto-Oncogene Proteins c-akt
  • Protein Binding
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Enzyme Activation
  • Endothelial Cells
 

Citation

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White, R. R., Roy, J. A., Viles, K. D., Sullenger, B. A., & Kontos, C. D. (2008). A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function. Angiogenesis, 11(4), 395–401. https://doi.org/10.1007/s10456-008-9122-4
White, Rebekah R., Julie A. Roy, Kristi D. Viles, Bruce A. Sullenger, and Christopher D. Kontos. “A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.Angiogenesis 11, no. 4 (2008): 395–401. https://doi.org/10.1007/s10456-008-9122-4.
White RR, Roy JA, Viles KD, Sullenger BA, Kontos CD. A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function. Angiogenesis. 2008;11(4):395–401.
White, Rebekah R., et al. “A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.Angiogenesis, vol. 11, no. 4, 2008, pp. 395–401. Pubmed, doi:10.1007/s10456-008-9122-4.
White RR, Roy JA, Viles KD, Sullenger BA, Kontos CD. A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function. Angiogenesis. 2008;11(4):395–401.
Journal cover image

Published In

Angiogenesis

DOI

EISSN

1573-7209

Publication Date

2008

Volume

11

Issue

4

Start / End Page

395 / 401

Location

Germany

Related Subject Headings

  • Umbilical Veins
  • Signal Transduction
  • Receptor, TIE-2
  • Proto-Oncogene Proteins c-akt
  • Protein Binding
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Humans
  • Enzyme Activation
  • Endothelial Cells