Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 50, Pages 21671-21676Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1016233107
Keywords
CAR peptide; angiogenesis; proteoglycan; cell-penetrating peptide
Categories
Funding
- National Cancer Institute [PO1 CA 82713, CA 30199]
- Department of Defense [DAMD17-02-1-0315, X81XWH-08-2-0032]
- Academy of Finland
- Sigrid Juselius Foundation
- Instrumentarium Research Foundation (Helsinki)
- Instrumentarium Research Foundation (Finland)
- Pirkanmaa Hospital District, Tampere University Hospital
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Permanent scars form upon healing of tissue injuries such as those caused by ischemia (myocardial infarction, stroke), trauma, surgery, and inflammation. Current options in reducing scar formation are limited to local intervention. We have designed a systemically administered, target-seeking biotherapeutic for scar prevention. It consists of a vascular targeting peptide that specifically recognizes angiogenic blood vessels and extravasates into sites of injury, fused with a therapeutic molecule, decorin. Decorin prevents tissue fibrosis and promotes tissue regeneration by inhibiting TGF-beta activity and by other regulatory activities. The decorin-targeting peptide fusion protein had substantially increased neutralizing activity against TGF-beta 1 in vitro compared with untargeted decorin. In vivo, the fusion protein selectively accumulated in wounds, and promoted wound healing and suppressed scar formation at doses where nontargeted decorin was inactive. These results show that selective targeting yields a tissue-healing and scar-reducing compound with enhanced specificity and potency. This approach may help make reducing scar formation by systemic drug delivery a feasible option for surgery and for the treatment of pathological processes in which scar formation is a problem.
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