Premium
Foamy virus‐adenovirus hybrid vectors for gene therapy of the arthritides
Author(s) -
Weber Conrad,
Armbruster Nicole,
Scheller Carsten,
Kreppel Florian,
Kochanek Stefan,
Rethwilm Axel,
Steinert Andre F.
Publication year - 2013
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2705
Subject(s) - transgene , genetic enhancement , transduction (biophysics) , gene delivery , biology , viral vector , interleukin 1 receptor antagonist , in vivo , green fluorescent protein , in vitro , microbiology and biotechnology , gene , receptor , receptor antagonist , antagonist , recombinant dna , genetics , biochemistry
Abstract Background Genetic treatments of chronic arthritic conditions are essentially dependent on safe and efficient vector systems. To combine features of the efficient transduction of adenovirus vectors with the advantage of stable integration into the host cell genome of apathogenic prototype foamy virus vectors, hybrid vectors (FAD) have been established. In the present study, we have generated and investigated the use of safe FAD vectors for direct gene delivery to joints. Methods We generated recombinant FAD encoding enhanced green fluorescent protein (EGFP) or human interleukin 1 receptor antagonist protein (IL1RA) cDNA, and explored their transgene expression profile, as well as the bioactivity of the IL1RA transgene in vitro . The feasibility of IL1RA gene delivery to articular tissues was investigated in a pilot study employing direct FAD injections to the knee joints of Wistar rats. Results FAD vectors efficiently transduced human or rat fibroblasts with EGFP or IL1RA transgene in vitro . Levels of IL1RA transgene expression were high, stable and functional in vitro . Transduced synovial fibroblasts and high levels of IL1RA protein (10–35 ng/ml) could be detected in vivo in the synovium of Wistar rats 3–5 days after injection of FAD vectors to the knee joints. Conclusions Our results indicate that FAD vectors are capable of efficient in vivo gene transfer to synovium and merit further investigation as a means of providing efficient and long‐term intra‐articular transgene expression for treatment of the arthritides. Copyright © 2013 John Wiley & Sons, Ltd.