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). 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.
Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Jialin
J
Song
Department of Neurology, Jinshan Hospital, Fudan University , Shanghai , China.
Yinghui
Y
Chen
Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, Shandong , China.
Shichao
S
Jiang
School of Pharmacy, Shanghai JiaoTong University , Shanghai , China.
Kejia
K
Yang
School of Pharmacy, Shanghai JiaoTong University , Shanghai , China.
Xiaoming
X
Li
School of Pharmacy, Shanghai JiaoTong University , Shanghai , China.
Xiaotian
X
Zhao
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.
Yuanming
Y
Ouyang
Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Cunyi
C
Fan
School of Pharmacy, Shanghai JiaoTong University , Shanghai , China.
Weien
W
Yuan
PDAPEI; RNA interference; TNF-α; rheumatoid arthritis