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Science 28 June 2002:
Vol. 296. no. 5577, pp. 2404 - 2407
DOI: 10.1126/science.1070200
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Reports

Tumor Regression by Targeted Gene Delivery to the Neovasculature

John D. Hood,1 Mark Bednarski,2 Ricardo Frausto,1 Samira Guccione,2 Ralph A. Reisfeld,1 Rong Xiang,1 David A. Cheresh1*

Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alpha vbeta 3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATPµ-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors.

1 Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Lucas Magnetic Resonance Spectroscopy Research Center, Stanford School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.
*   To whom correspondence should be addressed. E-mail: cheresh{at}scripps.edu

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