Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis

• Published in: Frontiers in immunology Vol. 7; p. 305
• Main Authors: Song, Jialin, Chen, Yinghui, Jiang, Shichao, Yang, Kejia, Li, Xiaoming, Zhao, Xiaotian, Ouyang, Yuanming, Fan, Cunyi, Yuan, Weien
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.08.2016
• Subjects: Immunology; RNA interference; TNF-α; rheumatoid arthritis; PDAPEI
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2016.00305

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.