Hillard Rubin
Genzyme
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Publication
Featured researches published by Hillard Rubin.
Gene Therapy | 2009
Peter Pechan; Hillard Rubin; Michael Lukason; J Ardinger; Elizabeth DuFresne; William W. Hauswirth; Samuel C. Wadsworth; Abraham Scaria
Vascular endothelial growth factor (VEGF) is important in pathological neovascularization, which is a key component of diseases such as the wet form of age-related macular degeneration, proliferative diabetic retinopathy and cancer. One of the most potent naturally occurring VEGF binders is VEGF receptor Flt-1. We have generated two novel chimeric VEGF-binding molecules, sFLT01 and sFLT02, which consist of the second immunoglobulin (IgG)-like domain of Flt-1 fused either to a human IgG1 Fc or solely to the CH3 domain of IgG1 Fc through a polyglycine linker 9Gly. In vitro analysis showed that these novel molecules are high-affinity VEGF binders. We have demonstrated that adeno-associated virus serotype 2 (AAV2)-mediated intravitreal gene delivery of sFLT01 efficiently inhibits angiogenesis in the mouse oxygen-induced retinopathy model. There were no histological observations of toxicity upon persistent ocular expression of sFLT01 for up to 12 months following intravitreal AAV2-based delivery in the rodent eye. Our data suggest that AAV2-mediated intravitreal gene delivery of our novel molecules may be a safe and effective treatment for retinal neovascularization.
Molecular Therapy | 2011
Michael Lukason; Elizabeth DuFresne; Hillard Rubin; Peter Pechan; Qiuhong Li; Ivana K. Kim; Szilard Kiss; Christina J. Flaxel; Margaret E Collins; Joan W. Miller; William W. Hauswirth; Timothy K. MacLachlan; Samuel C. Wadsworth; Abraham Scaria
Inhibition of vascular endothelial growth factor (VEGF) for the management of the pathological ocular neovascularization associated with diseases such as neovascular age-related macular degeneration is a proven paradigm; however, monthly intravitreal injections are required for optimal treatment. We have previously shown that a novel, secreted anti-VEGF molecule sFLT01 delivered by intravitreal injection of an AAV2 vector (AAV2-sFLT01) gives persistent expression and is efficacious in a murine model of retinal neovascularization. In the present study, we investigate transduction and efficacy of an intravitreally administered AAV2-sFLT01 in a nonhuman primate (NHP) model of choroidal neovascularization (CNV). A dose-dependent and persistent expression of sFLT01 was observed by collecting samples of aqueous humor at different time points over 5 months. The location of transduction as elucidated by in situ hybridization was in the transitional epithelial cells of the pars plana and in retinal ganglion cells. AAV2-sFLT01 was able to effectively inhibit laser-induced CNV in a dose-dependent manner as determined by comparing the number of leaking CNV lesions in the treated versus control eyes using fluorescein angiography. Our data suggest that intravitreal delivery of AAV2-sFLT01 may be an effective long-term treatment for diseases caused by ocular neovascularization.
Molecular therapy. Methods & clinical development | 2014
Peter Pechan; Jeffery Ardinger; Jyothi Ketavarapu; Hillard Rubin; Samuel C. Wadsworth; Abraham Scaria
Production of large quantities of viral vectors is crucial for the success of gene therapy in the clinic. There is a need for higher titers of herpes simplex virus-1 (HSV-1) vectors both for therapeutic use as well as in the manufacturing of clinical grade adeno-associated virus (AAV) vectors. HSV-1 yield increased when primary human fibroblasts were treated with anti-inflammatory drugs like dexamethasone or valproic acid. In our search for compounds that would increase HSV-1 yield, we investigated another anti-inflammatory compound, aurintricarboxylic acid (ATA). Although ATA has been previously shown to have antiviral effects, we find that low (micromolar) concentrations of ATA increased HSV-1 vector production yields. Our results showing the use of ATA to increase HSV-1 titers have important implications for the production of certain HSV-1 vectors as well as recombinant AAV vectors.
Archive | 2014
Peter Pechan; Jeffery Ardinger; Hillard Rubin; Samuel C. Wadsworth; Abraham Scaria
Molecular Therapy | 2004
Abraham Scaria; Peter Pechan; Michael Lukason; Hillard Rubin; Samuel C. Wadsworth
Investigative Ophthalmology & Visual Science | 2015
Peter Pechan; Jeffery Ardinger; Hillard Rubin; Michael Lukason; Elizabeth Barry; Seng Cheng; Abraham Scaria
Archive | 2014
Peter Pechan; Jeffery Ardinger; Hillard Rubin; Samuel C. Wadsworth; Abraham Scaria
Cancer Research | 2009
Rebecca G. Bagley; Min Yao; Leslie Kurtzberg; William Weber; Hillard Rubin; Kerry Culm-Merdek; Christine Burnett; Lucy Yen; Elizabeth Isenberger; Cindy Rogers; Cecile Rouleau; Peter Pechan; William Brondyk; Abraham Scaria; Johanne Kaplan; Beverly A. Teicher
Investigative Ophthalmology & Visual Science | 2008
William W. Hauswirth; R. Miller; Ji-jing Pang; V. Choido; A. Abraham; Peter Pechan; Hillard Rubin; Samuel C. Wadsworth; Q. Li
Molecular Therapy | 2006
Abraham Scaria; Peter Pechan; Hillard Rubin; Michael Lukason; Elizabeth Barry; Jeffrey Ardinger; Huawei Qiu; Qiuhong Li; James J. Peterson; William W. Hauswirth; Samuel C. Wadsworth