Journal
MOLECULAR THERAPY
Volume 21, Issue 1, Pages 119-130Publisher
CELL PRESS
DOI: 10.1038/mt.2012.131
Keywords
-
Categories
Funding
- Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I)
- Instituto de Salud Carlos III (FIS) [PI060122]
- Spanish Ministry of Science and Innovation (MICINN) [SAF2009-10691]
- Comunidad Autonoma de Madrid [S2006/BIO-0236, S2010/BMD-2312]
- MICINN [RECAVA RD06/0014/005]
- Fundacio La Marato de TV3 [080731]
Ask authors/readers for more resources
Administration of anti-inflammatory cytokines is a common therapeutic strategy in chronic inflammatory diseases. Gene therapy is an efficient method for delivering therapeutic molecules to target cells. Expression of the cell adhesion molecule E-selectin (ESEL), which is expressed in the early stages of inflammation, is controlled by proinflammatory cytokines, making its promoter a good candidate for the design of inflammation-regulated gene therapy vectors. This study describes an ESEL promoter (ESELp)-based lentiviral vector (LV) that drives localized transgene expression during inflammation. Mouse matrigel plug assays with ESELp-transduced endothelial cells showed that systemic lipopolysaccharide (LPS) administration selectively induces ESELp-controlled luciferase expression in vivo. Inflammation-specific induction was confirmed in a mouse model of arthritis, showing that this LV is repeatedly induced early in acute inflammation episodes and is downregulated during remission. Moreover, the local acute inflammatory response in this animal model was efficiently blocked by expression of the anti-inflammatory cytokine interleukin-10 (IL10) driven by our LV system. This inflammation-regulated expression system has potential application in the design of new strategies for the local treatment of chronic inflammatory diseases such as cardiovascular and autoimmune diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available