Human CD64-targeted non-viral siRNA delivery system for blood monocyte gene modulation
| Autor: | Jang Kyoung Kim, Yong-Hee Kim, Seok Beom Yong, Hyung-Jin Kim, Jee Young Chung |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Therapeutic gene modulation medicine.drug_class THP-1 Cells Mice SCID Gene delivery Monoclonal antibody Arginine Immunoglobulin G Monocytes Article 03 medical and health sciences Mice 0302 clinical medicine medicine Gene silencing Animals Humans RNA Small Interfering CD64 Multidisciplinary biology business.industry Monocyte Receptors IgG Gene Transfer Techniques 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Drug delivery Cancer research biology.protein RNA Interference business Oligopeptides Single-Chain Antibodies |
| Zdroj: | Scientific Reports SCIENTIFIC REPORTS(7) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|