The goal of this Phase I SBIR is the pre-clinical development of a novel gene-based delivery system for bevacizumab (anti-VEGF antibody) to treat wet age-related macular degeneration (AMD). The premise is based on: (1) the demonstrated efficacy of monthly intravitreal injections of the monoclonal bevacizumab in treating wet AMD that is accompanied by a high cost of drug and safety issues related to the requirements for frequent administration; and (2) our demonstration that intravitreal genetic delivery of bevacizumab with the adeno-associated virus (AAV) serotype rh.10 vector, AAVrh.10BevMab, provides long term protection from inappropriate VEGF-mediated retinal angiogenesis in mice. While efficacious, current therapy of repeated intravitreal administration of bevacizumab monoclonal therapy is associated with discomfort, significant risks and high cost and administration of this antibody leads to high peak levels that may be associated with toxicity and prolonged trough levels that are sub-therapeutic. This SBIR contains the following specific aims and milestones: Specific Aim 1. Assess the hypothesis that intravitreal administration of AAVrh.10BevMab can express therapeutic levels of bevacizumab in the eye of non-human primates. The milestone is to achieve therapeutic levels of biologically active bevacizumab with practical AAV dosing in terms of volume and vector concentration. Specific Aim 2. Based on the dose established in Specific Aim 1, assess the hypothesis that intravitreal delivery of AAVrh.10BevMab is effective in inhibiting laser induced neovascularization in non-human primates. This will provide the final supporting efficacy data, using a standard animal model, to allow design of a pivotal toxicology study to support FDA filing. A Phase II application will be submitted to support the pre- IND process and the product development and clinical trial.