Gene Therapy in the Cornea

Abstract

Abstract Several advantages are apparent in making the cornea particularly attractive for gene transfer: it has a well‐defined anatomy and is easily accessible during ambulatory visits, as well as surgical procedures. The most important, and most difficult, challenge in gene therapy is the issue of delivery. Although naked or plasmid deoxyribonucleic acid (DNA) has occasionally been applied into the corneal stroma, usually, DNA is complexed in a vector to enhance delivery into the cornea. To date, the most efficient method for delivering nucleic acid‐based treatments mainly involves viral vectors, including retrovirus, lentivirus, adeno‐associated virus and adenovirus. However, nonviral vectors (lipid‐ or polymeric‐based systems), although less efficient, are safer and its production is simpler and cheaper than viral vectors. Corneal diseases potentially treatable by gene therapy include mucopolysaccharidosis VII, herpetic stromal keratitis, corneal neovascularisation, corneal burns and corneal transplantation and graft rejection, among others. Key Concepts The cornea is an ideal target for gene therapy as it is accessible, relatively immune privileged and easily monitored owing to its transparency. The most important, and most difficult, challenge in corneal gene therapy is the issue of delivery. Corneal diseases potentially treatable by gene therapy include mucopolysaccharidosis VII, herpetic stromal keratitis, corneal neovascularisation, corneal burns and corneal transplantation and graft rejection, among others. Gene therapy in the cornea has been mainly studied in animal models, the clinical trials in humans being scarce.