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Gene replacement therapy for retinal CNG channelopathies

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Abstract

Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3′–5′-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

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References

  • Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28(1):92–95

    PubMed  CAS  Google Scholar 

  • Aguirre GD, Rubin LF (1974) Pathology of hemeralopia in the Alaskan malamute dog. Invest Ophthalmol 13(3):231–235

    PubMed  CAS  Google Scholar 

  • Aguirre GD, Rubin LF (1975) The electroretinogram in dogs with inherited cone degeneration. Invest Ophthalmol 14(11):840–847

    PubMed  CAS  Google Scholar 

  • Ahnelt PK, Kolb H (2000) The mammalian photoreceptor mosaic-adaptive design. Prog Retin Eye Res 19(6):711–777

    Article  PubMed  CAS  Google Scholar 

  • Ali RR, Sarra GM, Stephens C, Alwis MD, Bainbridge JW, Munro PM, Fauser S, Reichel MB, Kinnon C, Hunt DM, Bhattacharya SS, Thrasher AJ (2000) Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat Genet 25(3):306–310

    Article  PubMed  CAS  Google Scholar 

  • Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358(21):2231–2239

    Article  PubMed  CAS  Google Scholar 

  • Bareil C, Hamel CP, Delague V, Arnaud B, Demaille J, Claustres M (2001) Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum Genet 108(4):328–334

    Article  PubMed  CAS  Google Scholar 

  • Becirovic E, Nakova K, Hammelmann V, Hennel R, Biel M, Michalakis S (2010) The retinitis pigmentosa mutation c.3444+1G>A in CNGB1 results in skipping of exon 32. PLoS ONE 5(1):e8969

    Article  PubMed  Google Scholar 

  • Biel M, Michalakis S (2007) Function and dysfunction of CNG channels: insights from channelopathies and mouse models. Mol Neurobiol 35(3):266–277

    Article  PubMed  CAS  Google Scholar 

  • Biel M, Seeliger M, Pfeifer A, Kohler K, Gerstner A, Ludwig A, Jaissle G, Fauser S, Zrenner E, Hofmann F (1999) Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci USA 96(13):7553–7557

    Article  PubMed  CAS  Google Scholar 

  • Boye SE, Boye SL, Lewin AS, Hauswirth WW (2013) A comprehensive review of retinal gene therapy. Mol Ther 21(3):509–519

    Article  PubMed  CAS  Google Scholar 

  • Carvalho LS, Xu J, Pearson RA, Smith AJ, Bainbridge JW, Morris LM, Fliesler SJ, Ding XQ, Ali RR (2011) Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy. Hum Mol Genet 20(16):3161–3175

    Article  PubMed  CAS  Google Scholar 

  • Cideciyan AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang JJ, Sumaroka A, Windsor EA, Wilson JM, Flotte TR, Fishman GA, Heon E, Stone EM, Byrne BJ, Jacobson SG, Hauswirth WW (2008) Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci USA 105(39):15112–15117

    Article  PubMed  CAS  Google Scholar 

  • Cideciyan AV, Jacobson SG, Beltran WA, Sumaroka A, Swider M, Iwabe S, Roman AJ, Olivares MB, Schwartz SB, Komaromy AM, Hauswirth WW, Aguirre GD (2013) Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci USA 110(6):E517–E525

    Article  PubMed  CAS  Google Scholar 

  • Claes E, Seeliger M, Michalakis S, Biel M, Humphries P, Haverkamp S (2004) Morphological characterization of the retina of the CNGA3(−/−)Rho(−/−) mutant mouse lacking functional cones and rods. Invest Ophthalmol Vis Sci 45(6):2039–2048

    Article  PubMed  Google Scholar 

  • Deeb SS (2005) The molecular basis of variation in human color vision. Clin Genet 67(5):369–377

    Article  PubMed  CAS  Google Scholar 

  • Ding XQ, Harry CS, Umino Y, Matveev AV, Fliesler SJ, Barlow RB (2009) Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism. Hum Mol Genet 18(24):4770–4780

    Article  PubMed  CAS  Google Scholar 

  • Dong BA, Nakai H, Xiao WD (2010) Characterization of genome integrity for oversized recombinant AAV vector. Mol Ther 18(1):87–92

    Article  PubMed  CAS  Google Scholar 

  • Dryja TP, Finn JT, Peng YW, McGee TL, Berson EL, Yau KW (1995) Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc Natl Acad Sci USA 92(22):10177–10181

    Article  PubMed  CAS  Google Scholar 

  • Eksandh L, Kohl S, Wissinger B (2002) Clinical features of achromatopsia in Swedish patients with defined genotypes. Ophthalmic Genet 23(2):109–120

    Article  PubMed  Google Scholar 

  • Genead MA, Fishman GA, Rha J, Dubis AM, Bonci DM, Dubra A, Stone EM, Neitz M, Carroll J (2011) Photoreceptor structure and function in patients with congenital achromatopsia. Invest Ophthalmol Vis Sci 52(10):7298–7308

    Article  PubMed  CAS  Google Scholar 

  • Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368(9549):1795–1809

    Article  PubMed  CAS  Google Scholar 

  • Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, Conlon TJ, Boye SL, Flotte TR, Byrne BJ, Jacobson SG (2008) Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 19(10):979–990

    Article  PubMed  CAS  Google Scholar 

  • Hofmann F, Biel M, Kaupp UB; International Union of P (2003) International Union of Pharmacology. XLII. Compendium of voltage-gated ion channels: cyclic nucleotide-modulated channels. Pharmacol Rev 55(4):587–589

    Google Scholar 

  • Hofmann F, Biel M, Kaupp UB (2005) International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev 57(4):455–462

    Article  PubMed  CAS  Google Scholar 

  • Hüttl S, Michalakis S, Seeliger M, Luo DG, Acar N, Geiger H, Hudl K, Mader R, Haverkamp S, Moser M, Pfeifer A, Gerstner A, Yau KW, Biel M (2005) Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1. J Neurosci 25(1):130–138

    Article  PubMed  Google Scholar 

  • Jacobson SG, Cideciyan AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, Peden MC, Aleman TS, Boye SL, Sumaroka A, Conlon TJ, Calcedo R, Pang JJ, Erger KE, Olivares MB, Mullins CL, Swider M, Kaushal S, Feuer WJ, Iannaccone A, Fishman GA, Stone EM, Byrne BJ, Hauswirth WW (2012) Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol 130(1):9–24

    Article  PubMed  CAS  Google Scholar 

  • Jagla WM, Jagle H, Hayashi T, Sharpe LT, Deeb SS (2002) The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes. Hum Mol Genet 11(1):23–32

    Article  PubMed  CAS  Google Scholar 

  • Kalloniatis M, Fletcher EL (2004) Retinitis pigmentosa: understanding the clinical presentation, mechanisms and treatment options. Clin Exp Optom 87(2):65–80

    Article  PubMed  Google Scholar 

  • Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82(3):769–824

    PubMed  CAS  Google Scholar 

  • Kennan A, Aherne A, Humphries P (2005) Light in retinitis pigmentosa. Trends Genet 21(2):103–110

    Article  PubMed  CAS  Google Scholar 

  • Khan NW, Wissinger B, Kohl S, Sieving PA (2007) CNGB3 achromatopsia with progressive loss of residual cone function and impaired rod-mediated function. Invest Ophthalmol Vis Sci 48(8):3864–3871

    Article  PubMed  Google Scholar 

  • Koch S, Sothilingam V, Garcia Garrido M, Tanimoto N, Becirovic E, Koch F, Seide C, Beck SC, Seeliger MW, Biel M, Muhlfriedel R, Michalakis S (2012) Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Hum Mol Genet 21(20):4486–4496

    Article  PubMed  CAS  Google Scholar 

  • Kohl S, Marx T, Giddings I, Jagle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B (1998) Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet 19(3):257–259

    Article  PubMed  CAS  Google Scholar 

  • Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe LT, Wissinger B (2000) Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet 9(14):2107–2116

    Article  PubMed  CAS  Google Scholar 

  • Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jagle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B (2005) CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet 13(3):302–308

    Article  PubMed  CAS  Google Scholar 

  • Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD (2010) Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet 19(13):2581–2593

    Article  PubMed  CAS  Google Scholar 

  • Komaromy AM, Rowlan JS, Corr AT, Reinstein SL, Boye SL, Cooper AE, Gonzalez A, Levy B, Wen R, Hauswirth WW, Beltran WA, Aguirre GD (2013) Transient photoreceptor deconstruction by CNTF enhances rAAV-mediated cone functional rescue in late stage CNGB3-achromatopsia. Mol Ther 21(6):1131–1141

    Article  PubMed  CAS  Google Scholar 

  • Kondo H, Qin M, Mizota A, Kondo M, Hayashi H, Hayashi K, Oshima K, Tahira T, Hayashi K (2004) A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest Ophthalmol Vis Sci 45(12):4433–4439

    Article  PubMed  Google Scholar 

  • Kumar-Singh R (2008) Barriers for retinal gene therapy: separating fact from fiction. Vis Res 48(16):1671–1680

    Article  PubMed  CAS  Google Scholar 

  • Lai Y, Yue YP, Duan DS (2010) Evidence for the failure of adeno-associated virus serotype 5 to package a viral genome >=8.2 kb. Mol Ther 18(1):75–79

    Article  PubMed  CAS  Google Scholar 

  • Leconte L, Barnstable CJ (2000) Impairment of rod cGMP-gated channel alpha-subunit expression leads to photoreceptor and bipolar cell degeneration. Invest Ophthalmol Vis Sci 41(3):917–926

    PubMed  CAS  Google Scholar 

  • Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358(21):2240–2248

    Article  PubMed  CAS  Google Scholar 

  • Mallouk N, Ildefonse M, Pages F, Ragno M, Bennett N (2002) Basis for intracellular retention of a human mutant of the retinal rod channel alpha subunit. J Membr Biol 185(2):129–136

    Article  PubMed  CAS  Google Scholar 

  • Michalakis S, Geiger H, Haverkamp S, Hofmann F, Gerstner A, Biel M (2005) Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3. Invest Ophthalmol Vis Sci 46(4):1516–1524

    Article  PubMed  Google Scholar 

  • Michalakis S, Muhlfriedel R, Tanimoto N, Krishnamoorthy V, Koch S, Fischer MD, Becirovic E, Bai L, Huber G, Beck SC, Fahl E, Buning H, Paquet-Durand F, Zong X, Gollisch T, Biel M, Seeliger MW (2010) Restoration of cone vision in the CNGA3-/- mouse model of congenital complete lack of cone photoreceptor function. Mol Ther 18(12):2057–2063

    Article  PubMed  CAS  Google Scholar 

  • Michalakis S, Mühlfriedel RL, Tanimoto N, Krishnamoorthy V, Koch S, Beck SC, Buening H, Gollisch T, Biel M, Seeliger MW (2011a) Exploring different serotypes and promoters in rAAV-mediated gene replacement therapy of achromatopsia type 2 (ACHM2). ARVO Ann Meet Abstr Search Progr Plan 2011:490

  • Michalakis S, Zong X, Becirovic E, Hammelmann V, Wein T, Wanner KT, Biel M (2011b) The glutamic acid-rich protein is a gating inhibitor of cyclic nucleotide-gated channels. J Neurosci 31(1):133–141

    Article  PubMed  CAS  Google Scholar 

  • Michalakis S, Xu J, Biel M, Ding XQ (2013) Detection of cGMP in the degenerating retina. Methods Mol Biol 1020:235–245

    Article  PubMed  Google Scholar 

  • Pang JJ, Alexander J, Lei B, Deng W, Zhang K, Li Q, Chang B, Hauswirth WW (2010) Achromatopsia as a potential candidate for gene therapy. Adv Exp Med Biol 664:639–646

    Article  PubMed  CAS  Google Scholar 

  • Pang JJ, Deng WT, Dai X, Lei B, Everhart D, Umino Y, Li J, Zhang K, Mao S, Boye SL, Liu L, Chiodo VA, Liu X, Shi W, Tao Y, Chang B, Hauswirth WW (2012) AAV-mediated cone rescue in a naturally occurring mouse model of CNGA3-achromatopsia. PLoS ONE 7(4):e35250

    Article  PubMed  CAS  Google Scholar 

  • Peng C, Rich ED, Varnum MD (2004) Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. Neuron 42(3):401–410

    Article  PubMed  CAS  Google Scholar 

  • Petersen-Jones SM, Winkler PA, Bartoe JT, Venta PJ, Ekenstedt K (2013) Large animal model of autosomal recessive RP due to a CNGB1 gene mutation. ARVO Annu Meet Abstr Search Progr Plan 2013:684

  • Pokorny J, Smith VC, Pinckers AJ, Cozijnsen M (1982) Classification of complete and incomplete autosomal recessive achromatopsia. Graefes Arch Clin Exp Ophthalmol 219(3):121–130

    Article  PubMed  CAS  Google Scholar 

  • Reicher S, Seroussi E, Gootwine E (2010) A mutation in gene CNGA3 is associated with day blindness in sheep. Genomics 95(2):101–104

    Article  PubMed  CAS  Google Scholar 

  • Rubin LF (1971a) Clinical features of hemeralopia in the adult Alaskan malamute. J Am Vet Med Assoc 158(10):1696–1698

    PubMed  CAS  Google Scholar 

  • Rubin LF (1971b) Hemeralopia in Alaskan Malamute pups. J Am Vet Med Assoc 158(10):1699–1701

    PubMed  CAS  Google Scholar 

  • Sacks OW (1997) The island of the colourblind. AA Knopf, New York

  • Shamir MH, Ofri R, Bor A, Brenner O, Reicher S, Obolensky A, Averbukh E, Banin E, Gootwine E (2010) A novel day blindness in sheep: epidemiological, behavioural, electrophysiological and histopathological studies. Vet J 185(2):130–137

    Article  PubMed  Google Scholar 

  • Shuart NG, Haitin Y, Camp SS, Black KD, Zagotta WN (2011) Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels. Nat Commun 2:457

    Article  PubMed  Google Scholar 

  • Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 11(16):1823–1833

    Article  PubMed  CAS  Google Scholar 

  • Simpson DA, Clark GR, Alexander S, Silvestri G, Willoughby CE (2011) Molecular diagnosis for heterogeneous genetic diseases with targeted high-throughput DNA sequencing applied to retinitis pigmentosa. J Med Genet 48(3):145–151

    Article  PubMed  Google Scholar 

  • Sundin OH, Yang JM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH (2000) Genetic basis of total colourblindness among the Pingelapese islanders. Nat Genet 25(3):289–293

    Article  PubMed  CAS  Google Scholar 

  • Surace EM, Auricchio A (2008) Versatility of AAV vectors for retinal gene transfer. Vis Res 48(3):353–359

    Article  PubMed  CAS  Google Scholar 

  • Thiadens AA, Slingerland NW, Roosing S, van Schooneveld MJ, van Lith-Verhoeven JJ, van Moll-Ramirez N, van den Born LI, Hoyng CB, Cremers FP, Klaver CC (2009) Genetic etiology and clinical consequences of complete and incomplete achromatopsia. Ophthalmology 116(10):1984–1989, e1981

    Google Scholar 

  • Thiadens AA, Roosing S, Collin RW, van Moll-Ramirez N, van Lith-Verhoeven JJ, van Schooneveld MJ, den Hollander AI, van den Born LI, Hoyng CB, Cremers FP, Klaver CC (2010) Comprehensive analysis of the achromatopsia genes CNGA3 and CNGB3 in progressive cone dystrophy. Ophthalmology 117(4):825–830, e821

    Google Scholar 

  • Vandenberghe LH, Auricchio A (2012) Novel adeno-associated viral vectors for retinal gene therapy. Gene Ther 19(2):162–168

    Article  PubMed  CAS  Google Scholar 

  • Weitz D, Ficek N, Kremmer E, Bauer PJ, Kaupp UB (2002) Subunit stoichiometry of the CNG channel of rod photoreceptors. Neuron 36(5):881–889

    Article  PubMed  CAS  Google Scholar 

  • Wu ZJ, Yang HY, Colosi P (2010) Effect of genome size on AAV vector packaging. Mol Ther 18(1):80–86

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Morris L, Fliesler SJ, Sherry DM, Ding XQ (2011) Early-onset, slow progression of cone photoreceptor dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Invest Ophthalmol Vis Sci 52(6):3557–3566

    Article  PubMed  Google Scholar 

  • Yokoyama S (2000) Molecular evolution of vertebrate visual pigments. Prog Retin Eye Res 19(4):385–419

    Article  PubMed  CAS  Google Scholar 

  • Yu FH, Catterall WA (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE 2004 (253):re15

  • Zhang Y, Molday LL, Molday RS, Sarfare SS, Woodruff ML, Fain GL, Kraft TW, Pittler SJ (2009) Knockout of GARPs and the beta-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity. J Cell Sci 122(Pt 8):1192–1200

    Article  PubMed  CAS  Google Scholar 

  • Zheng J, Trudeau MC, Zagotta WN (2002) Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit. Neuron 36(5):891–896

    Article  PubMed  CAS  Google Scholar 

  • Zhong H, Molday LL, Molday RS, Yau KW (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420(6912):193–198

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Tistou and Charlotte Kerstan Foundation (RDCURE Project).

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  1. Center for Integrated Protein Science Munich, CIPSM and Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr 5-13, 81377, Munich, Germany

    Christian Schön, Martin Biel & Stylianos Michalakis

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  1. Christian Schön
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Correspondence to Stylianos Michalakis.

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Communicated by J. Graw.

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Schön, C., Biel, M. & Michalakis, S. Gene replacement therapy for retinal CNG channelopathies. Mol Genet Genomics 288, 459–467 (2013). https://doi.org/10.1007/s00438-013-0766-4

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