A CRISPR-based inducible system for VEGF repression for AMD
Tulane researchers have developed a CRISPR-based gene therapy targeting VEGF pathways for treating age-related macular degeneration (AMD). This innovative approach uses Cas9-Krab or dCas9-VP16 to silence lncEGFL7OS, a long non-coding RNA involved in angiogenesis, potentially offering a more durable alternative to current anti-VEGF injection therapies.
The Problem
Age-related macular degeneration affects 12 million Americans and is the leading cause of blindness in developed countries, accounting for 8.7% of global blindness. Current anti-VEGF treatments require repeated invasive intravitreal injections that lack durability and carry complication risks. Patients need a more effective, longer-lasting therapeutic option that reduces treatment burden and improves outcomes.
The Solution
This CRISPR-based therapeutic targets lncEGFL7OS found on two human genes involved in angiogenesis (EGFL7 and miR-126). The system uses CRISPR gene silencing in the lncEGFL7OS/EGFL7/miR-126 bidirectional promoter region, delivered via lentivirus. In vitro proof-of-concept demonstrates significant reduction in VEGF levels and decreased angiogenesis in human fibroblasts, suggesting potential for durable therapeutic effects with reduced injection frequency.
The Opportunity
The technology addresses the $38 billion ophthalmic disease treatment market, projected to reach $65 billion by 2030 at 7.8% CAGR. Anti-VEGF agents hold over 32% market share, with leading AMD drugs generating $1.5+ billion annually. This CRISPR approach offers competitive advantages through potentially longer-lasting effects, reduced injection frequency, and lower complication rates. Beyond AMD, the platform has potential applications for other VEGF-driven ocular diseases, expanding market opportunities in ophthalmology and gene therapy sectors.
