Samuel Jotham Reich
University of Pennsylvania
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Publication
Featured researches published by Samuel Jotham Reich.
Retina-the Journal of Retinal and Vitreous Diseases | 2004
Michael J. Tolentino; Alexander J. Brucker; Joshua Fosnot; Gui-shuang Ying; I.–H. Wu; Gulraiz Malik; S. Wan; Samuel Jotham Reich
Purpose To determine the safety and efficacy of small interfering RNA (siRNA) directed against vascular endothelial growth factor (VEGF) in a nonhuman primate model of laser-induced choroidal neovascularization (CNV). Methods Each animal received laser rupture of Bruch’s membrane to induce CNV in both eyes. Each animal was then randomized to receive 0.05 mL of either vehicle alone or VEGF siRNA at 70 &mgr;g, 150 &mgr;g, or 350 &mgr;g in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography, and fluorescein angiography for 36 days after laser injury. Electroretinograms were measured at baseline and at 5 weeks after laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized, and double-masked fashion on days 15, 22, 29, and 36 after laser. Results VEGF siRNA did not cause any change in electroretinographic, hemorrhage, inflammation, or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of CNV and attenuated angiographic leakage in a dose-dependent manner. Conclusion Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser-induced CNV in a nonhuman primate in a dose-dependent manner. This study demonstrates preclinical proof of a principle that supports proceeding to clinical studies of VEGF siRNA in patients with exudative age-related macular degeneration.
Human Gene Therapy | 2003
Samuel Jotham Reich; Alberto Auricchio; Markus Hildinger; Ernest Glover; Albert M. Maguire; James M. Wilson; Jean Bennett
Recombinant vectors based on adeno-associated virus (AAV) can efficiently transduce many different cell types, including cells of the retina, resulting in stable gene expression. A major shortcoming of this vector is its small packaging capacity. A trans-splicing approach, which reconstitutes gene expression from two independent AAV vectors, can be used to overcome the vectors packaging limitations. The efficiency of this system to date has been disappointing, and therefore its utility for therapeutic application limited. We demonstrate here that efficiency and cellular specificity of trans-splicing is dependent on selection of the appropriate AAV serotype. Efficiency of transgene expression resulting from trans-splicing in skeletal muscle approaches that obtained when delivering the intact transgene when using AAV2 vectors packaged with AAV5 capsids (AAV2/5). This expands the potential of AAV vectors for retinal gene therapy. The use of AAV2/5 also increases the efficiency of trans-splicing in photoreceptors. Selection of the appropriate AAV serotype is likely to affect efficiency of trans-splicing in other organ systems as well.
Journal of Virology | 2003
Enrico Maria Surace; Alberto Auricchio; Samuel Jotham Reich; Tonia S. Rex; Ernest Glover; Stacey Pineles; Waixing Tang; Erin O'Connor; Arkady Lyubarsky; Andrey Savchenko; Edward N. Pugh; Albert M. Maguire; James M. Wilson; Jean Bennett
ABSTRACT The development of fetal ocular gene transfer may be useful as a therapeutic tool for the prevention of retinal genetic disorders with congenital or early clinical manifestations. In this study we explored the neural progenitor transduction patterns of adeno-associated virus (AAV) vectors following delivery to the developing retina. Recombinant vectors with the same genome carrying the enhanced green fluorescent protein (EGFP) transgene packaged in capsids of differing serotypes (serotypes 1, 2, and 5, termed AAV2/1, AAV2/2, and AAV2/5, respectively) were created. Delivery of the AAV vectors during early retinal development resulted in efficient and stable transduction of retinal progenitors. Vector surface proteins and the developmental status of the retina profoundly affected viral tropism and transgene distribution. The procedure is not detrimental to retinal development and function and therefore provides a safe delivery vehicle for potential therapeutic applications and a means of assessing the mechanisms of retina development and disease.
Current Opinion in Genetics & Development | 2003
Samuel Jotham Reich; Jean Bennett
Recent advances in the field of ocular gene transfer have led researchers pursuing treatment for age-related macular degeneration and diabetic retinopathy to turn to gene therapy for the answer. Viral vector-mediated delivery of both anti-angiogenic proteins and molecules that inhibit the eyes endogenous pro-angiogenic factors has successfully diminished the pathology of ocular diseases in rodent models. A gene-therapy solution to the debilitating blindness caused by ocular neovascularization may be on the horizon.
Molecular Vision | 2003
Samuel Jotham Reich; J. Fosnot; A. Kuroki; Tang W; Xiaoping Yang; Albert M. Maguire; Jean Bennett; Michael J. Tolentino
Archive | 2006
Michael J. Tolentino; Samuel Jotham Reich
Archive | 2003
Samuel Jotham Reich; Enrico Maria Surace; Michael J. Tolentino
Archive | 2004
Samuel Jotham Reich; Michael J. Tolentino
Archive | 2004
Samuel Jotham Reich; Michael J. Tolentino
Archive | 2004
Samuel Jotham Reich; Michael J. Tolentino