Chemical control of protein stability and function in living mice

Laura A. Banaszynski, Mark A. Sellmyer, Christopher H. Contag, Thomas J. Wandless, Steve H. Thorne

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Conditional control of protein function in vivo offers great potential for deconvoluting the roles of individual proteins in complicated systems. We recently developed a method in which a small protein domain, termed a destabilizing domain, confers instability to fusion protein partners in cultured cells. Instability is reversed when a cell-permeable small molecule binds this domain. Here we describe the use of this system to regulate protein function in living mammals. We show regulation of secreted proteins and their biological activity with conditional secretion of an immunomodulatory cytokine, resulting in tumor burden reduction in mouse models. Additionally, we use this approach to control the function of a specific protein after systemic delivery of the gene that encodes it to a tumor, suggesting uses for enhancing the specificity and efficacy of targeted gene-based therapies. This method represents a new strategy to regulate protein function in living organisms with a high level of control.

Original languageEnglish (US)
Pages (from-to)1123-1127
Number of pages5
JournalNature Medicine
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Protein Stability
Proteins
Tumors
Genes
Mammals
Tumor Burden
Genetic Therapy
Bioactivity
Cultured Cells
Fusion reactions
Cytokines
Cells
Molecules
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Banaszynski, L. A., Sellmyer, M. A., Contag, C. H., Wandless, T. J., & Thorne, S. H. (2008). Chemical control of protein stability and function in living mice. Nature Medicine, 14(10), 1123-1127. https://doi.org/10.1038/nm.1754

Chemical control of protein stability and function in living mice. / Banaszynski, Laura A.; Sellmyer, Mark A.; Contag, Christopher H.; Wandless, Thomas J.; Thorne, Steve H.

In: Nature Medicine, Vol. 14, No. 10, 01.10.2008, p. 1123-1127.

Research output: Contribution to journalArticle

Banaszynski, LA, Sellmyer, MA, Contag, CH, Wandless, TJ & Thorne, SH 2008, 'Chemical control of protein stability and function in living mice', Nature Medicine, vol. 14, no. 10, pp. 1123-1127. https://doi.org/10.1038/nm.1754
Banaszynski, Laura A. ; Sellmyer, Mark A. ; Contag, Christopher H. ; Wandless, Thomas J. ; Thorne, Steve H. / Chemical control of protein stability and function in living mice. In: Nature Medicine. 2008 ; Vol. 14, No. 10. pp. 1123-1127.
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