GENE DELIVERY OF A VIRAL ANTI-INFLAMMATORY PROTEIN TO COMBAT OCULAR INFLAMMATION.
Submitted by Cristhian J Ildefonso on
Title | GENE DELIVERY OF A VIRAL ANTI-INFLAMMATORY PROTEIN TO COMBAT OCULAR INFLAMMATION. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Ildefonso, CJ, Jaime, H, Rahman, MM, Li, Q, Boye, SE, Hauswirth, WW, Lucas, AR, McFadden, G, Lewin, AS |
Journal | Hum Gene Ther |
Date Published | 2014 Nov 24 |
ISSN | 1557-7422 |
Abstract | Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with the pro-inflammatory signaling pathways involving both the NLRP3 inflammasome and NF-κB. We have developed and characterized an adeno-associated virus (AAV) vector that delivers a secretable and cell penetrating form of the M013 protein (TatM013). The expressed TatM013 protein was secreted and blocked the endotoxin-induced secretion of IL-1β in monocyte derived cells and the reactive aldehyde induced secretion of IL-1β in RPE cells. The local anti-inflammatory effects of AAV-delivered TatM013 were evaluated in an endotoxin induced uveitis (EIU) mouse model following intravitreal injection of mice with an AAV2-based vector containing either TatM013 fused to a secreted GFP tag (sGFP-TatM013) or GFP. Expression of the sGFP-TatM013 transgene was demonstrated by fluorescence fundoscopy in living mice. In EIU, the number of infiltrating cells and the concentration of IL-1β in the vitreous body was significantly lower in the eyes injected with AAV-sGFP-TatM013 than in the eyes injected with control AAV-GFP. These results suggest that a virus-derived inhibitor of the innate immune response, when delivered via AAV, could be a generalized therapy for various inflammatory diseases of the eye. |
DOI | 10.1089/hum.2014.089 |
Alternate Journal | Hum. Gene Ther. |
PubMed ID | 25420215 |
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