Frontiers in Immunology (Aug 2016)

Efficient and nontoxic biological response carrier delivering TNF-α shRNA for gene silencing in a murine model of rheumatoid arthritis

  • Jialin Song,
  • Yinghui Chen,
  • Shichao Jiang,
  • Kejia Yang,
  • Xiaoming Li,
  • Xiaotian Zhao,
  • yuanming Ouyang,
  • Cunyi Fan,
  • Weien Yuan

DOI
https://doi.org/10.3389/fimmu.2016.00305
Journal volume & issue
Vol. 7

Abstract

Read online

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.

Keywords