V. Chiodo
University of Florida
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Featured researches published by V. Chiodo.
PLOS ONE | 2013
Karina E. Guziewicz; Barbara Zangerl; András M. Komáromy; V. Chiodo; Sanford L. Boye; William W. Hauswirth; William A. Beltran; Gustavo D. Aguirre
Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In this study, the specificity, efficiency and safety of rAAV-mediated transgene expression driven by the human VMD2 promoter were assessed in wild-type canine retinae. While the subretinal delivery of rAAV2/1 vector serotype was associated with cone damage in the retina when BEST1 and GFP were co-expressed, the rAAV2/2 vector serotype carrying either GFP reporter or BEST1 transgene under control of human VMD2 promoter was safe, and enabled specific transduction of the RPE cell monolayer that was stable for up to 6 months post injection. These encouraging studies with the rAAV2/2 vector lay the groundwork for development of gene augmentation therapy for human bestrophinopathies.
Gene Therapy | 2008
András M. Komáromy; John J. Alexander; A. E. Cooper; V. Chiodo; L. G. Glushakova; Gregory M. Acland; William W. Hauswirth; Gustavo D. Aguirre
Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP in the longand medium-wavelength-absorbing cones (L/M cones) of normal and diseased retinas. The PR0.5 promoter was not effective. Adding three copies of the 35-bp LCR in front of PR0.5 lead to weak GFP expression in L/M cones. The HB569 promoter was not specific, and GFP was expressed in a few L/M cones, some rods and the retinal pigment epithelium. These results suggest that L/M cones, the predominant class of cone photoreceptors in the retinas of dogs and most mammalian species can be successfully targeted using the human red cone opsin promoter.
Molecular Therapy | 2006
Samuel G. Jacobson; Gregory M. Acland; Gustavo D. Aguirre; Tomas S. Aleman; Sanford L. Boye; Sharon B. Schwartz; Artur V. Cideciyan; Caroline J. Zeiss; András M. Komáromy; Alejandro J. Roman; Elizabeth A. M. Windsor; Alexander Sumaroka; Susan E. Pearce-Kelling; Thomas J. Conlon; Q. Li; V. Chiodo; Terence R. Flotte; Albert M. Maguire; Jean Bennett; William W. Hauswirth
Top of pageAbstract Introduction: AAV2 delivery of the RPE65 cDNA to the retina of blind RPE65-deficient dogs or rd12 mice restores vision as determined electrophysiologically and behaviorally. This strategy is being considered for human trials in RPE65-associated Leber congenital amaurosis, but safety and dose-efficacy within a non-toxic range with this vector have not been defined. Here we report the results of toxicology and biodistribution studies in two mammalian species, dogs and rats. Methods: Vector related pathology and spread after subretinal delivery of AAV2-CBA-RPE65 was studied in RPE65-mutant dogs and normal Spague-Dawley rats. Doses of vector delivered bracketed those intended for the clinical study. Results: There was no systemic toxicity at any vector dose in either species. In dogs ocular examinations showed mild or moderate inflammation that resolved over an initial 3-month period. Retinal histopathology indicated that traumatic lesions from the injection were common, but retinal thinning within the injection region only occurred at the highest vector doses. Biodistribution studies were also performed in RPE65-mutant dogs at various times after vector injection and in normal rats at about 2 weeks and 2 months post-injection. Vector DNA was not widespread outside the injected eye with blood and gonadal tissue consistently negative. Concomitant dose-response results in the RPE65-mutant dogs indicated that the highest 1.5 log unit range of vector doses was efficacious. Conclusions: Given the efficacy and toxicity limits defined in this study, a range for safe vector dose escalation of subretinal AAV2-CBA-RPE65 is suggested for initial human trials.
Molecular Therapy | 2006
Samuel G. Jacobson; Gregory M. Acland; Gustavo D. Aguirre; Tomas S. Aleman; Sharon B. Schwartz; Artur V. Cideciyan; Caroline J. Zeiss; András M. Komáromy; Shalesh Kaushal; Alejandro J. Roman; Elizabeth A. M. Windsor; Alexander Sumaroka; Susan E. Pearce-Kelling; Thomas J. Conlon; V. Chiodo; Sanford L. Boye; Terence R. Flotte; Albert M. Maguire; Jean Bennett; William W. Hauswirth
Investigative Ophthalmology & Visual Science | 2008
András M. Komáromy; John J. Alexander; V. Chiodo; Monique M. Garcia; Jacqueline C. Tanaka; Cheryl M. Craft; Gregory M. Acland; William W. Hauswirth; Gustavo D. Aguirre
Investigative Ophthalmology & Visual Science | 2007
András M. Komáromy; John J. Alexander; V. Chiodo; William W. Hauswirth; Gregory M. Acland; Gustavo D. Aguirre
Investigative Ophthalmology & Visual Science | 2006
J. Liu; Seok-Hong Min; V. Chiodo; Sanford L. Boye; John J. Alexander; M. Ding; Thomas J. Doyle; S. Mani; Alfred S. Lewin; William W. Hauswirth
Investigative Ophthalmology & Visual Science | 2011
Karina E. Guziewicz; András M. Komáromy; William W. Hauswirth; Sanford L. Boye; V. Chiodo; Julianna Slavik; Gustavo D. Aguirre; Barbara Zangerl
Investigative Ophthalmology & Visual Science | 2010
Ajay Sharma; Jonathan Tovey; John W. Cowden; V. Chiodo; William W. Hauswirth; Rajiv R. Mohan
Investigative Ophthalmology & Visual Science | 2009
András M. Komáromy; Jessica S. Rowlan; John J. Alexander; V. Chiodo; William W. Hauswirth; Gregory M. Acland; Gustavo D. Aguirre