AUTHOR=Song Jialin , Chen Yinghui , Jiang Shichao , Yang Kejia , Li Xiaoming , Zhao Xiaotian , Ouyang Yuanming , Fan Cunyi , Yuan Weien 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00305

DOI=10.3389/fimmu.2016.00305

ISSN=1664-3224

ABSTRACT=Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and nontoxic 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. 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 (CIA). PDAPEI delivered TNF-α shRNA has great potential in the treatment of rheumatoid arthritis.