Skip NavigationSkip to Content
Return Return to Search Results

Immunological priming potentiates non-viral anti-inflammatory gene therapy treatment of neuropathic pain

  1. Author:
    Sloane, E.
    Langer, S.
    Jekich, B.
    Mahoney, J.
    Hughes, T.
    Frank, M.
    Seibert, W.
    Huberty, G.
    Coats, B.
    Harrison, J.
    Klinman, D.
    Poole, S.
    Maier, S.
    Johnson, K.
    Chavez, R.
    Watkins, L. R.
    Leinw, L.
    Milligan, E.

  2. Author Address

    Sloane, E.; Jekich, B.; Mahoney, J.; Frank, M.; Seibert, W.; Huberty, G.; Coats, B.; Harrison, J.; Maier, S.; Watkins, L. R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Sloane, E.; Jekich, B.; Mahoney, J.; Frank, M.; Seibert, W.; Huberty, G.; Coats, B.; Harrison, J.; Maier, S.; Watkins, L. R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA. [Langer, S.; Hughes, T.; Leinwand, L.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Klinman, D.] NCI, Frederick, MD 21701 USA. [Poole, S.] Natl Inst Biol Stand & Controls, Potters Bar, Herts, England. [Johnson, K.; Chavez, R.] Avigen Inc, Alameda, CA USA. [Milligan, E.] Univ New Mexico, Hlth Sci Ctr, Dept Neurosci, Albuquerque, NM 87131 USA.
    1. Year: 2009
  2. Journal: Gene Therapy
    1. 16
    2. 10
    3. Pages: 1210-1222
  4. Type of Article: Article
  1. Abstract:

    We recently described a non-viral gene therapy paradigm offering long-term resolution of established neuropathic pain in several animal models. Here, the requirements for long-term therapeutic effects are described, and evidence is provided for a mechanism of action based on immunological priming of the intrathecal (i.t.) space. Long-term pain reversal was achieved when two i.t. injections of various naked plasmid DNA doses were separated by 5 h to 3 days. We show that an initial DNA injection, regardless of whether a transgene is included, leads to an accumulation of phagocytic innate immune cells. This accumulation coincides with the time in which subsequent DNA injection efficacy is potentiated. We show the ability of non-coding DNA to induce short-term pain reversal that is dependent on endogenous interleukin-10 (IL-10) signaling. Long-term efficacy requires the inclusion of an IL-10(F129S) transgene in the second injection. Blockade of IL-10, by a neutralizing antibody, either between the two injections or after the second injection induces therapeutic failure. These results show that this gene therapy paradigm uses an initial 'priming' injection of DNA to induce accumulation of phagocytic immune cells, allowing for potentiated efficacy of a subsequent 'therapeutic' DNA injection in a time- and dose-dependent manner. Gene Therapy (2009) 16, 1210-1222, doi: 10.1038/gt.2009.79, published online 2 July 2009

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1038/gt.2009.79
  3. PMID: 19571887

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel