Peptide versus gene therapy: Cathelicidin LL-37 and HSV-1 corneal infection

We compared the performance of biosynthetic corneal implants based on collagen-phosphorylcholine (Coll-MPC) with anti–Herpes Simplex Virus (HSV)-1 activity achieved by sustained release of the cathelicidin LL-37 from incorporated nanoparticles, to cell-based delivery of the peptide from human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 to confer viral resistance expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size. LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti–HSV-1 activity by blocking binding. While both slowed down virus spread, neither was able on its own to completely inhibit the viruses.