| Description |
Age-Related Macular Degeneration (AMD), a chronic disease of the eye and leading cause of blindness in Americans over 50, is often treated with agents that inhibit Vascular Endothelial Growth Factor (VEGF). Ranibizumab is an anti-VEGF antibody fragment (Fab) effective at treating over 90% of AMD patients who receive the treatment via intravitreal injection. However, these injections are uncomfortable and frequent due to rapid clearance of the Fab from the eye (t1/2 ~ 9 days). This contributes to poor patient compliance. This project aims to extend the intraocular half-life of ranibizumab, thereby increasing patient compliance, by conjugating ECM targeting peptides to ranibizumab. A collagen binding peptide (CBP) and hyaluronic acid binding peptide (HABP) were synthesized to target type II collagen (Col) and hyaluronic acid (HA), respectively. These targets were chosen as they are abundant components of the vitreous. CBP and HABP were synthesized, purified, and chemically conjugated to ranibizumab. An ELISA-like assay examining VEGF binding showed comparable binding affinities of the two conjugated ranibizumab Fab proteins to that of unmodified ranibizumab, indicating that VEGF binding is not negatively impacted by peptide conjugation. Further, ELISA-like assays demonstrated binding of each conjugate to either HA or Col and VEGF, simultaneously. We expect that the conjugated binding peptides will slow clearance of ranibizumab from the eye, reducing the required injection frequency, thus improving compliance and leading to better therapeutic outcomes. |
