We chose to use a murine model of retinitis pigmentosa (the rds+/− mouse) for our first disease rescue studies. The protein product of this gene, RDS (retinal degeneration slow; also called Peripherin/rds or Peripherin 2), is a tetraspanin glycoprotein known to form homomeric complexes as well as heteromeric complexes with a related tetraspanin protein, rod outer segment membrane protein 1 (ROM-1). RDS is photoreceptor-specific and is critical for photoreceptor disc rim assembly, outer segment (OS) orientation, photoreceptor structural stability, and OS disc renewal [17]–[19]. Over 80 different mutations in the RDS gene have been identified in humans and are associated with multiple retinal diseases, including autosomal dominant retinitis pigmentosa (adRP) and progressive macular degeneration (MD) [20]–[23]. Unlike the retina in the homozygous (rds −/−) mouse, which fails to form OSs and undergoes fairly rapid apoptotic photoreceptor cell death, the retina in the heterozygous (rds+/−) mouse exhibits a classic, well-defined adRP phenotype characterized by early onset rod degeneration and late onset cone degeneration. Furthermore, the OSs of the rds+/− are highly disordered, malformed, and short (compared to normal OSs), are electrophysiologically deficient, and express reduced levels of key phototransduction proteins [24]–[27]. Of relevance to our strategy of gene supplementation, we and others have shown that expression of at least 80% of the normal amount of RDS is necessary in order to build proper photoreceptor OSs [24], [28].