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- Title
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors.
- Authors
Erwei Song; Pengcheng Zhu; Sang-Kyung Lee; Chowdhury, Dipanjan; Kussman, Steven; Dykxhoorn, Derek M; Yi Feng; Palliser, Deborah; Weiner, David B; Shankar, Premlata; Marasco, Wayne A; Lieberman, Judy
- Abstract
Delivery of small interfering RNAs (siRNAs) into cells is a key obstacle to their therapeutic application. We designed a protamine-antibody fusion protein to deliver siRNA to HIV-infected or envelope-transfected cells. The fusion protein (F105-P) was designed with the protamine coding sequence linked to the C terminus of the heavy chain Fab fragment of an HIV-1 envelope antibody. siRNAs bound to F105-P induced silencing only in cells expressing HIV-1 envelope. Additionally, siRNAs targeted against the HIV-1 capsid gene gag, inhibited HIV replication in hard-to-transfect, HIV-infected primary T cells. Intratumoral or intravenous injection of F105-P-complexed siRNAs into mice targeted HIV envelope-expressing B16 melanoma cells, but not normal tissue or envelope-negative B16 cells; injection of F105-P with siRNAs targeting c-myc, MDM2 and VEGF inhibited envelope-expressing subcutaneous B16 tumors. Furthermore, an ErbB2 single-chain antibody fused with protamine delivered siRNAs specifically into ErbB2-expressing cancer cells. This study demonstrates the potential for systemic, cell-type specific, antibody-mediated siRNA delivery.
- Subjects
CELL receptors; BINDING sites; IMMUNOGLOBULINS; RNA; T cells; LYMPHOCYTES
- Publication
Nature Biotechnology, 2005, Vol 23, Issue 6, p709
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt1101