Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?

Arthritis Research & Therapy
F A J van de LooW B van den Berg

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints, with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-alpha therapies (e.g. soluble tumour necrosis factor receptors) ameliorate disease in 60-70% of patients with RA. However, the need for repeated systemic administration of relatively high doses in order to achieve constant therapeutic levels in the joints, and the reported side effects are downsides to this systemic approach. Several gene therapeutic approaches have been developed to ameliorate disease in animal models of arthritis either by restoring the cytokine balance or by genetic synovectomy. In this review we summarize strategies to improve transduction of synovial cells, to achieve stable transgene expression using integrating viruses such as adeno-associated viruses, and to achieve transcriptionally regulated expression so that drug release can meet the variable demands imposed by the intermittent course of RA. Evidence from animal models convincingly supports the application of gene therapy in RA, and the feasibility of gene therapy was recently demonstrated in phase I clinical trials.

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·A W VarleyR S Munford
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·G BandaraC H Evans
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S S MakarovJ H Schwab
Oct 23, 1997·The Journal of Clinical Investigation·H ZhangY Chen
Oct 23, 1997·Nature Biotechnology·A W VarleyR S Munford
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·A V MiagkovS S Makarov
May 26, 1999·Rheumatology·D A Walsh
Aug 19, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·S WatanabeR Hirsch
Nov 1, 2000·Arthritis Research·P P TakG S Firestein
Nov 30, 2000·Arthritis Research·U Müller-Ladner, K Nishioka
Nov 30, 2000·Arthritis Research·R Holmdahl
Feb 24, 2001·Arthritis and Rheumatism·P H GoossensT W Huizinga
May 26, 2001·The Journal of Clinical Investigation·A NakajimaC G Fathman
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·Q YaoT J Oligino
Aug 18, 2001·Arthritis and Rheumatism·P P TakG S Firestein
Dec 12, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·J D WhalenC H Evans
Jan 12, 2002·The American Journal of Pathology·Yuji YamanishiGary S Firestein
Mar 29, 2002·Arthritis and Rheumatism·Jong-Mook KimSunyoung Kim

❮ Previous
Next ❯

Citations

Aug 26, 2006·Nature Clinical Practice. Rheumatology·Falk MoritzSteffen Gay
Nov 10, 2005·Arthritis Research & Therapy·Yuti Chernajovsky
Nov 16, 2007·Arthritis Research & Therapy·Miguel Otero, Mary B Goldring
May 5, 2007·Expert Opinion on Biological Therapy·Adrienn AngyalGabriella Sármay
May 27, 2006·Arthritis and Rheumatism·Christopher H EvansPaul D Robbins
Jul 27, 2006·Arthritis and Rheumatism·Christian S HaasAlisa E Koch
Nov 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Myew-Ling TohPierre Miossec
Feb 28, 2019·Journal of Cellular Physiology·Mahdi ZavvarMohammad H Nicknam

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
transgenic
prophylactic treatment
gene knockout
biopsies

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.