AAV2-sFLT01: An Investigational Gene Therapy for Ocular Neovascularization

1. Introduction to AAV2-sFLT01

1.1. Overview of AAV2-sFLT01 as an Investigational Gene Therapy

AAV2-sFLT01 is an investigational gene therapy product that was developed to address ocular diseases characterized by abnormal blood vessel growth (neovascularization). The therapeutic agent consists of a recombinant, replication-defective adeno-associated virus serotype 2 (AAV2) vector.[1] AAV vectors are a common choice in gene therapy due to their ability to transduce a variety of cell types, including the non-dividing cells of the retina, and their generally favorable safety profile, which includes a lack of known human pathogenicity and a tendency for the delivered genetic material to remain episomal (not integrating into the host genome).[1] The AAV2-sFLT01 vector is engineered to carry and express the sFLT01 gene, which codes for a soluble anti-angiogenic protein.[1] The primary route of administration investigated for AAV2-sFLT01 was intravitreal (IVT) injection, a common and minimally invasive method for delivering therapeutics directly into the vitreous cavity of the eye, allowing the agent to diffuse and reach target tissues in the posterior segment.[1]

1.2. Therapeutic Rationale: Targeting Vascular Endothelial Growth Factor (VEGF)

The therapeutic strategy underlying AAV2-sFLT01 centers on the inhibition of Vascular Endothelial Growth Factor (VEGF), particularly VEGF-A. VEGF-A is a potent signaling protein that plays a crucial role in stimulating angiogenesis and increasing vascular permeability. These processes are key pathological drivers in several common and severe ocular diseases.[1]