Gene Therapy for Choroideremia: in Vitro Rescue Mediated by Recombinant Adenovirus

Choroideremia (CHM) is an X-linked retinal degenerative disease resulting from a lack of functional Rab Escort Protein-1 (REP-1). As a first step in developing gene-based therapies for this disease, we evaluated the feasibility of delivering functional REP-1 to defective lymphocytes and fibroblasts isolated from individuals with CHM. A recombinant adenovirus delivering the full-length human cDNA encoding REP-1 under the control of a cytomegalovirus promoter was generated. Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo.