Gene Therapy for Mouse Models of ADRP

  • Marina S. Gorbatyuk
  • William W. Hauswirth
  • Alfred S. Lewin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

Autosomal Dominant Retinitis Pigmentosa (ADRP) is caused by mutations in the rhodopsin gene (RHO) in 30% of patients, and dominant negative mutations are often associated with toxicity of the mutated protein. Preventing or retarding ADRP progression may require the repair or silencing of the defective RHO gene. Two strategies for RHO mRNA silencing have recently been proposed (Millington-Ward et al., 1997; Lewin and Hauswirth, 2001). They are based on the application of therapeutic molecules such as ribozymes (Rz) and small interfering RNA (siRNA) that inhibit RHO expression.


Gene Therapy Retinitis Pigmentosa Retinal Degeneration Outer Nuclear Layer Dominant Negative Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Cashman, S.M., Binkley, E.A., and Kumar-Singh, R., 2005, Towards mutation-independent silencing of genes involved in retinal degeneration by RNA interference, Gene Ther., 12: 1223.CrossRefGoogle Scholar
  2. Gorbatyuk, M.S., Pang, J.J., Thomas, J., Jr., Hauswirth, W.W., and Lewin, A.S., 2005, Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach, Mol. Vis., 11: 648.Google Scholar
  3. Gorbatyuk, M., Justilien, V., Liu, J., Hauswirth, W.W., and Lewin, A.S., 2007, Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme, Exp. Eye Res., 84: 44.CrossRefGoogle Scholar
  4. Kiang, A.S., Palfi, A., Ader, M., Kenna, P.F., Millington-Ward, S., Clark,G., Kennan, A., O’Reilly, M., Tam, L.C., Aherne, A., McNally, N., Humphries, P., and Farrar, G.J., 2005, Toward a gene therapy for dominant disease: validation of an RNA interference-based mutation-independent approach, Mol. Ther., 12: 555.CrossRefGoogle Scholar
  5. Kijas, J.W., Cideciyan, A.V., Aleman, T.S., Pianta, M.J., Pearce-Kelling, S.E., Miller, B.J., Jacobson, S.G., Aguirre, G.D., and Acland, G.M., 2002, Naturally occurring rhodopsin mutation in the dogcauses retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa, Proc. Natl. Acad. Sci. U.S.A., 99: 6328.CrossRefGoogle Scholar
  6. LaVail, M.M., Yasumura, D., Matthes, M.T., Drenser, K.A., Flannery, J.G., Lewin, A.S., and Hauswirth, W.W., 2000, Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy, Proc. Natl. Acad. Sci. U.S.A., 97: 11488.PubMedCrossRefGoogle Scholar
  7. Lewin, A.S. and Hauswirth, W.W., 2001, Ribozyme gene therapy: applications for molecular medicine, Trends Mol. Med., 7: 221.CrossRefGoogle Scholar
  8. Machida, S., Kondo, M., Jamison, J.A., Khan, N.W., Kononen, L.T., Sugawara, T., Bush, R.A., and Sieving, P.A., 2000, P23H rhodopsin transgenic rat: correlation of retinal function with histopathology, Invest. Ophthalmol. Vis. Sci., 41: 3200.Google Scholar
  9. Millington-Ward, S., O’Neill, B., Tuohy, G., al Jandal, N., Kiang, A.S., Kenna, P.F., Palfi, A., Hayden, P., Mansergh, F., Kennan, A., Humphries, P., and Farrar, G.J., 1997, Strategems in vitro for gene therapies directed to dominant mutations, Hum. Mol.Genet., 6: 1415.CrossRefGoogle Scholar
  10. Tessitore, A., Parisi, F., Denti, M.A., Allocca, M., Di Vicino, U., Domenici, L., Bozzoni, I., and Auricchio, A., 2006, Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model, Mol. Ther., 14: 692.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Marina S. Gorbatyuk
    • 1
  • William W. Hauswirth
    • 1
  • Alfred S. Lewin
    • 2
  1. 1.Department of Molecular Genetics and MicrobiologyUniversity of Florida College of MedicineGainesvilleUSA
  2. 2.Departments of Molecular Genetics and the Center for Vision Science, Department of Molecular Genetics and MicrobiologyUniversity of Florida, University of Florida College of MedicineGainesvilleUSA

Personalised recommendations