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Adeno-Associated Viral Vectors and the Retina

  • John J. Alexander
  • William W. Hauswirth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 613)

There are a variety of diseases of the retina arising from genetic and non-genetic causes, or a combination of both, that lead to the loss of vision. The retina is a prime location for gene therapy because of its accessibility, immune privileged status (Caspi, 2006), and susceptible cell types. Several strategies have been attempted to rescue retinal disease, including gene replacement (Acland et al., 2001), gene knockdown with both ribozymes (Gorbatyuk et al., 2007) and siRNA (Kiang et al., 2005), and therapeutic gene supplementation (Deng et al., 2005).

Keywords

Gene Therapy rAAV Vector Ubiquitous Promoter Vitelliform Macular Dystrophy Gene Therapy Experiment 
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.

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References

  1. Acland, G.M., Aguirre, G.D., Bennett, J., Aleman, T.S., Cideciyan, A.V., Bennicelli, J. et al. 2005, Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol. Ther. 12: 1072&–1082.PubMedCrossRefGoogle Scholar
  2. Acland, G.M., Aguirre, G.D., Ray, J., Zhang, Q., Aleman, T.S., Cideciyan, A.V. et al. 2001, Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28: 92&–95.PubMedCrossRefGoogle Scholar
  3. Atchison, R.W., Casto, B.C., and Hammon, W.M. 1965, Adenovirus-associated defective virus particles. Science 149: 754&–756.PubMedCrossRefGoogle Scholar
  4. Auricchio, A., Kobinger, G., Anand, V., Hildinger, M., O’Connor, E., Maguire, A.M. et al. 2001, Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. Hum. Mol. Genet. 10: 3075&–3081.PubMedCrossRefGoogle Scholar
  5. Bantel-Schaal, U. and zur Hausen, H. 1984, Characterization of the DNA of a defective human parvovirus isolated from a genital site. Virology 134: 52&–63.PubMedCrossRefGoogle Scholar
  6. Berns, K.I. and Giraud, C. 1996, Biology of adeno-associated virus. Curr. Top. Microbiol. Immunol. 218: 1&–23.PubMedGoogle Scholar
  7. Boulanger, A., Liu, S., Henningsgaard, A.A., Yu,S., and Redmond, T.M. 2000, The upstream region of the Rpe65 gene confers retinal pigment epithelium-specific expression in vivo and in vitro and contains critical octamer and E-box binding sites. J. Biol. Chem. 275: 31274&–31282.PubMedCrossRefGoogle Scholar
  8. Caspi, R.R. 2006, Ocular autoimmunity: the price of privilege? Immunol. Rev. 213: 23&–35.PubMedCrossRefGoogle Scholar
  9. Choi, V.W., McCarty, D.M., and Samulski, R.J. 2005, AAV hybrid serotypes: improved vectors for gene delivery. Curr. Gene Ther. 5: 299&–310.PubMedCrossRefGoogle Scholar
  10. Deng, W.T., Yan, Z., Dinculescu, A., Pang, J., Teusner, J.T., Cortez, N.G. et al. 2005, Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. Hum. Gene Ther. 16: 1247&–1254.PubMedCrossRefGoogle Scholar
  11. Dinculescu, A., Glushakova, L., Min, S.H., and Hauswirth, W.W. 2005, Adeno-associated virus-vectored gene therapy for retinal disease. Hum. Gene Ther. 16: 649&–663.PubMedCrossRefGoogle Scholar
  12. Esumi, N., Oshima, Y., Li,Y., Campochiaro, P.A., and Zack, D.J. 2004, Analysis of the VMD2 promoter and implication of E-box binding factors in its regulation. J. Biol. Chem. 279: 19064&–19073.PubMedCrossRefGoogle Scholar
  13. Flannery, J.G., Zolotukhin, S., Vaquero, M.I., LaVail, M.M., Muzyczka, N., and Hauswirth, W.W. 1997, Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc. Natl. Acad. Sci. U. S. A. 94: 6916&–6921.PubMedCrossRefGoogle Scholar
  14. Glushakova, L.G., Timmers, A.M., Pang, J., Teusner, J.T., and Hauswirth, W.W. 2006, Human blue-opsin promoter preferentially targets reporter gene expression to rat s-cone photoreceptors. Invest Ophthalmol. Vis. Sci. 47: 3505&–3513.PubMedCrossRefGoogle Scholar
  15. 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&–52.PubMedCrossRefGoogle Scholar
  16. Gu, S.M., Thompson, D.A., Srikumari, C.R., Lorenz, B., Finckh, U., Nicoletti, A. et al. 1997, Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat. Genet. 17: 194&–197.PubMedCrossRefGoogle Scholar
  17. Guy, J., Qi,X., Muzyczka, N., and Hauswirth, W.W. 1999, Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve. Arch. Ophthalmol. 117: 929&–937.PubMedGoogle Scholar
  18. Hauswirth, W.W. and Berns, K.I. 1977, Origin and termination of adeno-associated virus DNA replication. Virology 78: 488&–499.PubMedCrossRefGoogle Scholar
  19. Hermonat, P.L. and Muzyczka, N. 1984, Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Proc. Natl. Acad. Sci. U. S. A. 81: 6466&–6470.PubMedCrossRefGoogle Scholar
  20. Huttner, N.A., Girod, A., Perabo, L., Edbauer, D., Kleinschmidt, J.A., Buning, H., and Hallek, M. 2003, Genetic modifications of the adeno-associated virus type 2 capsid reduce the affinity and the neutralizing effects of human serum antibodies. Gene Ther. 10: 2139&–2147.PubMedCrossRefGoogle Scholar
  21. Jacobson, S.G., Acland, G.M., Aguirre, G.D., Aleman, T.S., Schwartz, S.B., Cideciyan, A.V. et al. 2006a, Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection. Mol. Ther. 13: 1074&–1084.Google Scholar
  22. Jacobson, S.G., Boye, S.L., Aleman, T.S., Conlon, T.J., Zeiss, C.J., Roman, A.J. et al. 2006b, Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis. Hum. Gene Ther. 17: 845&–858.Google Scholar
  23. Kiang, A.S., Palfi, A., Ader, M., Kenna, P.F., Millington-Ward, S., Clark, G. et al. 2005, Toward a gene therapy for dominant disease: validation of an RNA interference-based mutation-independent approach. Mol. Ther. 12: 555&–561.PubMedCrossRefGoogle Scholar
  24. Marlhens, F., Bareil, C., Griffoin, J.M., Zrenner, E., Amalric, P., Eliaou, C. et al. 1997, Mutations in RPE65 cause Leber’s congenital amaurosis. Nat. Genet. 17: 139&–141.PubMedCrossRefGoogle Scholar
  25. McCarty, D.M., Young, S.M., Jr., and Samulski, R.J. 2004, Integration of adeno-associated virus (AAV) and recombinant AAV vectors. Annu. Rev. Genet. 38: 819&–845.PubMedCrossRefGoogle Scholar
  26. Min, S.H., Molday, L.L., Seeliger, M.W., Dinculescu, A., Timmers, A.M., Janssen, A. et al. 2005, Prolonged recovery of retinal structure/function after gene therapy in an Rs1h-deficient mouse model of x-linked juvenile retinoschisis. Mol. Ther. 12: 644&–651.PubMedCrossRefGoogle Scholar
  27. Muzyczka, N. and Berns, K.I. 2001, Chapter 69, Fields Virology. Lippincott Williams & Wilkins.Google Scholar
  28. Rolling, F. 2004, Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives. Gene Ther. 11 Suppl 1: S26&–S32.PubMedCrossRefGoogle Scholar
  29. Sun, H., Tsunenari, T., Yau, K.W., and Nathans, J. 2002, The vitelliform macular dystrophy protein defines a new family of chloride channels. Proc. Natl. Acad. Sci. U. S. A. 99: 4008&–4013.PubMedCrossRefGoogle Scholar
  30. Warrington, K.H., Jr. and Herzog, R.W. 2006, Treatment of human disease by adeno-associated viral gene transfer. Hum. Genet. 119: 571&–603.PubMedCrossRefGoogle Scholar
  31. Wu, Z., Asokan, A., and Samulski, R.J. 2006, Adeno-associated virus serotypes: vector toolkit for human gene therapy. Mol. Ther. 14: 316&–327.PubMedCrossRefGoogle Scholar
  32. Yue, Y. and Duan, D. 2003, Double strand interaction is the predominant pathway for intermolecular recombination of adeno-associated viral genomes. Virology 313: 1&–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Molecular Genetics & MicrobiologyUniversity of Florida College of MedicineGainesville

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