The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissue.
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).


CONCLUSIONS
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.
Goossens
P H
PH
Leiden University Medical Center, The Netherlands.
Vogels
R
R
Pieterman
E
E
Havenga
M J
MJ
Bout
A
A
Breedveld
F C
FC
Valerio
D
D
Huizinga
T W
TW
D000256:Adenoviridae / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000628:therapy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D013582:Synovial Fluid / Q000502:physiology*; D013583:Synovial Membrane / Q000821:virology*
D007128:Immunoglobulin Fragments