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 language | English |
|---|---|
| Pages (from-to) | 709-717 |
| Number of pages | 9 |
| Journal | Nature Biotechnology |
| Volume | 23 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 9 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Microbiology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors
AU - Song, Erwei
AU - Zhu, Pengcheng
AU - Lee, Sang Kyung
AU - Chowdhury, Dipanjan
AU - Kussman, Steven
AU - Dykxhoorn, Derek M
AU - Feng, Yi
AU - Palliser, Deborah
AU - Weiner, David B.
AU - Shankar, Premlata
AU - Marasco, Wayne A.
AU - Lieberman, Judy
PY - 2005/12/9
Y1 - 2005/12/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=23844474160&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23844474160&partnerID=8YFLogxK
U2 - 10.1038/nbt1101
DO - 10.1038/nbt1101
M3 - Article
C2 - 15908939
AN - SCOPUS:23844474160
VL - 23
SP - 709
EP - 717
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
IS - 6
ER -