Abstract
This brief review summarizes the major proof-of-concept gene therapy studies for autosomal dominant retinitis pigmentosa (RP) caused by mutations in the rhodopsin gene (RHO-adRP) that have been conducted over the past 20 years in various animal models. We have listed in tabular form the various approaches, gene silencing reagents, gene delivery strategies, and salient results from these studies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bakondi B, Lv W, Lu B et al (2016) In vivo CRISPR/Cas9 gene editing corrects retinal dystrophy in the S334ter-3 rat model of autosomal dominant retinitis pigmentosa. Mol Ther 24:556–563
Botta S, Marrocco E, de Prisco N et al (2016) Rhodopsin targeted transcriptional silencing by DNA-binding. elife 5:e12242
Burnight ER, Gupta M, Wiley LA et al (2017) Using CRISPR-Cas9 to generate gene-corrected autologous iPSCs for the treatment of inherited retinal degeneration. Mol Ther 25:1999–2013
Chadderton N, Millington-Ward S, Palfi A et al (2009) Improved retinal function in a mouse model of dominant retinitis pigmentosa following AAV-delivered gene therapy. Mol Ther 17:593–599
Cideciyan AV, Sudharsan R, Dufour VL et al (2018) Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector. Proc Natl Acad Sci U S A 115:E8547–E8556
Dryja TP, McGee TL, Reichel E et al (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366
Gorbatyuk M, Justilien V, Liu J et al (2007a) Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme. Exp Eye Res 84:44–52
Gorbatyuk M, Justilien V, Liu J et al (2007b) Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery. Vis Res 47:1202–1208
Gorbatyuk MS, Pang JJ, Thomas J Jr et al (2005) Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach. Mol Vis 11:648–656
Kiang AS, Palfi A, Ader M et al (2005) Toward a gene therapy for dominant disease: validation of an RNA interference-based mutation-independent approach. Mol Ther 12:555–561
Latella MC, Di Salvo MT, Cocchiarella F et al (2016) In vivo editing of the human mutant rhodopsin gene by electroporation of plasmid-based CRISPR/Cas9 in the mouse retina. Mol Ther Nucleic Acids 5:e389
LaVail MM, Yasumura D, Matthes MT et al (2000) Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy. Proc Natl Acad Sci U S A 97:11488–11493
Lewin AS, Drenser KA, Hauswirth WW et al (1998) Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa. Nat Med 4:967–971
Mao H, Gorbatyuk MS, Rossmiller B et al (2012) Long-term rescue of retinal structure and function by rhodopsin RNA replacement with a single adeno-associated viral vector in P23H RHO transgenic mice. Hum Gene Ther 23:356–366
Mao H, James T Jr, Schwein A et al (2011) AAV delivery of wild-type rhodopsin preserves retinal function in a mouse model of autosomal dominant retinitis pigmentosa. Hum Gene Ther 22:567–575
Murray SF, Jazayeri A, Matthes MT et al (2015) Allele-specific inhibition of rhodopsin with an antisense oligonucleotide slows photoreceptor cell degeneration. Invest Ophthalmol Vis Sci 56:6362–6375
Mussolino C, Sanges D, Marrocco E et al (2011) Zinc-finger-based transcriptional repression of rhodopsin in a model of dominant retinitis pigmentosa. EMBO Mol Med 3:118–128
O’Reilly M, Millington-Ward S, Palfi A et al (2008) A transgenic mouse model for gene therapy of rhodopsin-linked retinitis pigmentosa. Vis Res 48:386–391
O’Reilly M, Palfi A, Chadderton N et al (2007) RNA interference-mediated suppression and replacement of human rhodopsin in vivo. Am J Hum Genet 81:127–135
Palfi A, Chadderton N, O’Reilly M et al (2015) Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho(−/−) mouse. Mol Ther Methods Clin Dev 2:15016
Palfi A, Millington-Ward S, Chadderton N et al (2010) Adeno-associated virus-mediated rhodopsin replacement provides therapeutic benefit in mice with a targeted disruption of the rhodopsin gene. Hum Gene Ther 21:311–323
Tessitore A, Parisi F, Denti MA et al (2006) Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model. Mol Ther 14:692–699
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
Sudharsan, R., Beltran, W.A. (2019). Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_19
Download citation
DOI: https://doi.org/10.1007/978-3-030-27378-1_19
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-27377-4
Online ISBN: 978-3-030-27378-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)