Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis

J Rheumatol. 1998 Jun;25(6):1118-25.


Objective: To evaluate the feasibility of direct in vivo gene transfer in an animal model of arthritis using a retroviral vector.

Methods: The timing and dose of retroviral vector was examined using very high titer retroviral vector (> or = 10(9) CFU) in rat adjuvant arthritis. Retroviral vector expressing beta-galactosidase (beta-gal) or vehicle alone was injected into the right ankle of rats with adjuvant arthritis. Ankles were injected either on Day 7 (pre-arthritis), Day 10 (early arthritis), Day 15 (accelerating arthritis), or Day 28 (chronic arthritis) after adjuvant immunization. Joints were harvested 3 days later and extracts were assayed for beta-gal activity.

Results: Synovial beta-gal expression was minimal in the Day 7 group and elevated in the Day 10, Day 15, and Day 28 groups. Gene transfer with retroviral vector did not exacerbate the local inflammatory response. Minimal or no beta-gal expression was observed in the contralateral uninjected paw or in the spleen, lung, liver, and kidneys. Frozen sections of retroviral vector injected joints were stained with X-gal and revealed transduced cells in the lining and superficial sublining layers. To determine the longevity of gene expression, ankle joints were injected with vector on Day 15 post-adjuvant, harvested, and assayed for beta-gal activity for up to 49 days after injection. Expression of the enzyme peaked from Day 3 to 7 and was still readily detected up to 49 days after retrovirus infection.

Conclusion: This is the first report of successful direct in vivo gene transfer in the rat adjuvant arthritis model using a retroviral vector. Appropriate timing of administration and very high titer retroviral vector preparations are key determinants of adequate gene transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle Joint / pathology
  • Ankle Joint / virology
  • Arthritis, Experimental / enzymology*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / virology
  • Cells, Cultured
  • Gene Transfer Techniques*
  • Genetic Vectors*
  • Humans
  • Lac Operon
  • Male
  • Rats
  • Rats, Inbred Lew
  • Retroviridae / genetics*
  • Synovial Membrane / virology*
  • beta-Galactosidase / metabolism


  • beta-Galactosidase