Human CD64-targeted non-viral siRNA delivery system for blood monocyte gene modulation.
A subset of phagocytes including inflammatory monocytes in blood migrate and give rise to macrophages in inflammatory tissues which generated the idea that blood monocytes are the therapeutic targets for drug delivery. Fc gamma receptor I (CD64) is a membrane receptor for the Fc region of immunoglobulin G, primarily expressed on monocyte-lineage, and H22 a monoclonal antibody for human CD64 had shown rapid blood monocyte binding and occupation in clinical studies. Small interfering RNA-mediated gene silencing as a therapeutic has been proposed and is a promising strategy in terms of its "knock-down" ability on the target gene prior to translation. However, its instability and off-targeting effect must be overcome for success in clinical studies. In this study, we developed a non-viral delivery system composed of oligo-nona-arginine (9R) and anti-human CD64 single chain antibodies (H22) for human monocyte-specific siRNA delivery. A targeted and efficient siRNA delivery mediated by anti-CD64 scFv-9R was observed in CD64 positive human leukemia cells, THP-1. With primary human blood cells, anti-CD64 scFv-9R mediated gene silencing was quantitatively confirmed representing blood monocyte selective gene delivery. These results demonstrate the potential of anti-CD64 scFv-9R mediated siRNA delivery for the treatment of human inflammatory diseases via blood monocytes gene delivery.
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, BK 21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 133-791 Seoul, Republic of Korea.
Seok-Beom
SB
Yong
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, BK 21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 133-791 Seoul, Republic of Korea.
Hyung Jin
HJ
Kim
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, BK 21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 133-791 Seoul, Republic of Korea.
Jang Kyoung
JK
Kim
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, BK 21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 133-791 Seoul, Republic of Korea.
Jee Young
JY
Chung
Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, BK 21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, 133-791 Seoul, Republic of Korea.
Yong-Hee
YH
Kim
D000818:Animals; D001120:Arginine / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000235:genetics; D000074084:THP-1 Cells
D009842:Oligopeptides; D034741:RNA, Small Interfering; D017452:Receptors, IgG; D057127:Single-Chain Antibodies; D001120:Arginine