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In vivo selection of tumor-targeting RNA motifs

Nature Chemical Biology volume 6, pages 22–24 (2010)Cite this article

Abstract

In an effort to target the in vivo context of tumor-specific moieties, we screened a large library of nuclease-resistant RNA oligonucleotides in tumor-bearing mice to identify candidate molecules with the ability to localize to hepatic colon cancer metastases. One of the selected molecules is an RNA aptamer that binds to p68, an RNA helicase that has been shown to be upregulated in colorectal cancer.

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Figure 1: CT26 intrahepatic tumor-evolved in vivo RNA selection pools.
Figure 2: Identification of tumor-specific protein.
Figure 3: Overlapping localization of aptamer 14-16 and p68 expression.

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Acknowledgements

We thank Z.R. Liu for kindly providing the p68-expressing plasmid pHM6 (Georgia State University) and Y. Wang for his insightful suggestions. We thank Y. Zhao, Z. Vujaskovic, H. Guo, Z. Mi and D. Wang for their technical assistance. We also are grateful to C. Kontos and X. Zhang for their critical reading of this manuscript. This work was supported by the Elsa U. Pardee Foundation (J.M.), an American Cancer Society pilot award (J.M.) and US National Institutes of Health grants NIH-5U19-AI-067798-04 (Z.N.R.) and NIH-R01-CA129190 (B.A.S.).

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

    Jing Mi, Yingmiao Liu, Johannes H Urban, Bruce A Sullenger & Bryan M Clary

  2. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA

    Zahid N Rabbani

  3. Department of Internal Medicine, Moses Cone Memorial Hospital, Greensboro, North Carolina, USA

    Zhongguang Yang

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  1. Jing Mi
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  4. Zhongguang Yang
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  6. Bruce A Sullenger
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Contributions

J.M. designed and performed the research investigations described and wrote the manuscript. Y.L. and J.H.U. contributed to the in vitro binding and gel-shift assays. Z.N.R. performed the fluorescent and immunohistochemical work in mice and cells. Z.Y. provided useful reagents, assisted in imaging of cells and tissues, and analyzed the data. B.A.S. provided supervision, including the conduct of and interpretation of the investigations, and edited the manuscript. B.M.C. generated the conceptual basis for performing in vivo selection as a means of interrogating the in vivo environment, provided supervision, including the conduct of and interpretation of the investigations, and edited the manuscript.

Corresponding authors

Correspondence to Bruce A Sullenger or Bryan M Clary.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 317 kb)

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Mi, J., Liu, Y., Rabbani, Z. et al. In vivo selection of tumor-targeting RNA motifs. Nat Chem Biol 6, 22–24 (2010). https://doi.org/10.1038/nchembio.277

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