Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis
Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA)...
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Published in | Frontiers in immunology Vol. 7; p. 305 |
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Main Authors | , , , , , , , , |
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19.08.2016
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Abstract | Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. |
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AbstractList | Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. |
Author | Yang, Kejia Li, Xiaoming Song, Jialin Zhao, Xiaotian Chen, Yinghui Ouyang, Yuanming Fan, Cunyi Jiang, Shichao Yuan, Weien |
AuthorAffiliation | 5 Shanghai Sixth People’s Hospital East Campus, Shanghai University of Medicine and Health , Shanghai , China 1 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital , Shanghai , China 4 School of Pharmacy, Shanghai JiaoTong University , Shanghai , China 3 Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, Shandong , China 2 Department of Neurology, Jinshan Hospital, Fudan University , Shanghai , China |
AuthorAffiliation_xml | – name: 4 School of Pharmacy, Shanghai JiaoTong University , Shanghai , China – name: 1 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital , Shanghai , China – name: 5 Shanghai Sixth People’s Hospital East Campus, Shanghai University of Medicine and Health , Shanghai , China – name: 2 Department of Neurology, Jinshan Hospital, Fudan University , Shanghai , China – name: 3 Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, Shandong , China |
Author_xml | – sequence: 1 givenname: Jialin surname: Song fullname: Song, Jialin organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China – sequence: 2 givenname: Yinghui surname: Chen fullname: Chen, Yinghui organization: Department of Neurology, Jinshan Hospital, Fudan University , Shanghai , China – sequence: 3 givenname: Shichao surname: Jiang fullname: Jiang, Shichao organization: Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, Shandong , China – sequence: 4 givenname: Kejia surname: Yang fullname: Yang, Kejia organization: School of Pharmacy, Shanghai JiaoTong University , Shanghai , China – sequence: 5 givenname: Xiaoming surname: Li fullname: Li, Xiaoming organization: School of Pharmacy, Shanghai JiaoTong University , Shanghai , China – sequence: 6 givenname: Xiaotian surname: Zhao fullname: Zhao, Xiaotian organization: School of Pharmacy, Shanghai JiaoTong University , Shanghai , China – sequence: 7 givenname: Yuanming surname: Ouyang fullname: Ouyang, Yuanming organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; Shanghai Sixth People's Hospital East Campus, Shanghai University of Medicine and Health, Shanghai, China – sequence: 8 givenname: Cunyi surname: Fan fullname: Fan, Cunyi organization: Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China – sequence: 9 givenname: Weien surname: Yuan fullname: Yuan, Weien organization: School of Pharmacy, Shanghai JiaoTong University , Shanghai , China |
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Copyright | Copyright © 2016 Song, Chen, Jiang, Yang, Li, Zhao, Ouyang, Fan and Yuan. 2016 Song, Chen, Jiang, Yang, Li, Zhao, Ouyang, Fan and Yuan |
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Keywords | RNA interference TNF-α rheumatoid arthritis PDAPEI |
Language | English |
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Title | Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis |
URI | https://www.ncbi.nlm.nih.gov/pubmed/27594856 https://search.proquest.com/docview/1817064336 https://pubmed.ncbi.nlm.nih.gov/PMC4990551 |
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