LIST OF FIGURES Figure page 1. Trans-acting ribozymes can be designed to specifically cleave an mRNA substrate........................................................................................................ 4 2. The secondary structure of self-splicing introns ..................................................7 3. The design of a trans-splicing group I intron for gene therapy applications ........9 4. The splicing mechanism of the group II intron..................................................11 5. Cleavage of the tRNA 5' leader sequence by RNase P......................................13 6. An RNA guide sequence allows the cleavage of a specific mRNA sequence by RN ase P................................................ ...................................................... 14 7. Self-cleaving ribozymes resolve concatemers formed by rolling-circular replication into individual genomic molecules............................................. 17 8. The structure of the trans-cleaving HDV ribozyme ..........................................18 9. The structure of the trans-cleaving hammerhead ribozyme................................19 10. The structure of the trans-cleaving hairpin ribozyme.........................................21 11. Structure of the rod photoreceptor cell ..............................................................26 12. Rod cells are intimately associated with RPE cells............................................27 13. Structure of the rod opsin protein......................................................................28 14. The visual transduction cascade .......................................................................29 15. Retinitis Pigmentosa results in a gradual loss of peripheral vision.....................31 16. The G90D mutation disrupts a salt bridge required for the normal structure of the rod opsin protein......................................... ................................................ 34 17. The nucleotide and amino acid sequence of the transgenes used to create the m ouse m odels for this project...................................................................................37 vi