The Influence of Synovial Fluid on Adenovirus-Mediated Gene Transfer to the Synovial Tissue

Arthritis Rheum. 2001 Jan;44(1):48-52. doi: 10.1002/1529-0131(200101)44:1<48::AID-ANR7>3.0.CO;2-D.

Abstract

Objective: To determine the effect of synovial fluid (SF) from rheumatoid arthritis (RA) patients on adenovirus type 5 (Ad5)-mediated gene transfer to synoviocytes, and to explore new strategies for vector development based on the neutralization data obtained.

Methods: SF was derived from 63 randomly selected R4 patients. Ten samples were used to study the effect of SF on Ad5-mediated gene transfer in synoviocytes. IgG and <100-kd fractions were purified from these 10 SF, and their effect on gene transfer was determined. Neutralizing activity against wild-type Ad5 (wt-Ad5), wt-Ad26, wt-Ad34, wt-Ad35, and wt-Ad48 was tested in the SF from the remaining 53 patients.

Results: Seven of 10 SF samples inhibited Ad5-mediated gene transfer. Purified antibodies exhibited inhibition patterns similar to those seen with unfractionated SF. In 5 of 10 SF samples, low molecular weight fractions inhibited gene transfer at low dilutions. Neutralization of wt-Ad35 by SF from RA patients was less frequent than neutralization of other wt-Ad tested (4% versus 42-72%; n = 53).

Conclusion: SF from 70% of the RA patients contained neutralizing antibodies that hamper Ad5-mediated gene transfer to synoviocytes. The activity of neutralizing antibodies may be circumvented in the majority of RA patients when vectors based on an Ad35 backbone are used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Arthritis, Rheumatoid / therapy
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Genetic Vectors / administration & dosage
  • Humans
  • Immunoglobulin Fragments / pharmacology
  • Synovial Fluid / physiology*
  • Synovial Membrane / virology*

Substances

  • Immunoglobulin Fragments