Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors

Erwei Song, Pengcheng Zhu, Sang Kyung Lee, Dipanjan Chowdhury, Steven Kussman, Derek M Dykxhoorn, Yi Feng, Deborah Palliser, David B. Weiner, Premlata Shankar, Wayne A. Marasco, Judy Lieberman

Research output: Contribution to journalArticle

809 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalNature Biotechnology
Volume23
Issue number6
DOIs
StatePublished - Dec 9 2005
Externally publishedYes

Fingerprint

Cell Surface Receptors
RNA
Antibodies
Small Interfering RNA
Protamines
HIV
HIV-1
Fusion reactions
Cells
Proteins
T-cells
gag Genes
Single-Chain Antibodies
Immunoglobulin Fab Fragments
Experimental Melanomas
Tumors
Capsid
Genes
Intravenous Injections
Tissue

ASJC Scopus subject areas

  • Microbiology

Cite this

Song, E., Zhu, P., Lee, S. K., Chowdhury, D., Kussman, S., Dykxhoorn, D. M., ... Lieberman, J. (2005). Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nature Biotechnology, 23(6), 709-717. https://doi.org/10.1038/nbt1101

Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. / Song, Erwei; Zhu, Pengcheng; Lee, Sang Kyung; Chowdhury, Dipanjan; Kussman, Steven; Dykxhoorn, Derek M; Feng, Yi; Palliser, Deborah; Weiner, David B.; Shankar, Premlata; Marasco, Wayne A.; Lieberman, Judy.

In: Nature Biotechnology, Vol. 23, No. 6, 09.12.2005, p. 709-717.

Research output: Contribution to journalArticle

Song, E, Zhu, P, Lee, SK, Chowdhury, D, Kussman, S, Dykxhoorn, DM, Feng, Y, Palliser, D, Weiner, DB, Shankar, P, Marasco, WA & Lieberman, J 2005, 'Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors', Nature Biotechnology, vol. 23, no. 6, pp. 709-717. https://doi.org/10.1038/nbt1101
Song, Erwei ; Zhu, Pengcheng ; Lee, Sang Kyung ; Chowdhury, Dipanjan ; Kussman, Steven ; Dykxhoorn, Derek M ; Feng, Yi ; Palliser, Deborah ; Weiner, David B. ; Shankar, Premlata ; Marasco, Wayne A. ; Lieberman, Judy. / Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. In: Nature Biotechnology. 2005 ; Vol. 23, No. 6. pp. 709-717.
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