Granted Patent
B2
US 12,605,466 · App. 17/436,510 · Granted Apr 21, 2026
Enhanced human opsin promoter for rod specific expression
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present disclosure provides short enhanced human opsin promoters for rod-specific expression that satisfy a need in the art for promoters that are able to control transgene expression both efficiently and selectively in rod cells, with little to no off-target expression in other photoreceptor cells. The disclosure provides vector constructs comprising transgenes operably controlled by this enhanced human opsin promoter that may be delivered and targeted with high specificity to rod cells. The disclosure also provides compositions comprising these vector constructs and methods for administration of these compositions to subjects in need thereof.
Claims (16)
1 . A recombinant viral vector comprising a polynucleotide encoding a transgene operably linked to a promoter that has a nucleotide sequence having at least 95% sequence identity to SEQ ID NO: 16 and 100% sequence identity to positions 29-35 of SEQ ID NO: 16.
2 . The viral vector of claim 1 , wherein the promoter has a nucleotide sequence comprising SEQ ID NO: 16.
3 . The viral vector of claim 1 , wherein the transgene is a CNGB1.
4 . The viral vector of claim 1 , wherein the transgene comprises a nucleotide sequence that is at least 90% identical to the nucleotide sequence of a human CNGB1, RHO, PRPF31, RP1, NRL, NR2E3, PDE6A, PDE6B, PDE6G, RP25, CNGA1, MAK, or ABCA4.
5 . The viral vector of claim 1 , wherein the transgene comprises a nucleotide sequence of about 4.0 to about 5.0 Kb in length.
6 . The viral vector of claim 1 , wherein the operably linked promoter and transgene are flanked by AAV inverted terminal repeat sequences (ITRs).
7 . The viral vector of claim 6 , wherein the ITRs are AAV2 ITRs.
8 . The viral vector of claim 1 , further comprising an enhancer element.
9 . The viral vector of claim 1 , wherein the transgene comprises a nucleotide sequence that is at least 90% identical to the sequence of a human CNGB1.
10 . An rAAV particle comprising the viral vector of claim 1 .
11 . A composition comprising the rAAV particle of claim 9 and a pharmaceutically acceptable carrier, diluent or excipient.
12 . A method comprising administering the composition of claim 11 to a subject having a retinal disease, disorder or condition, wherein the disease, disorder or condition is retinitis pigmentosa, rod dystrophy, wet age-related macular degeneration, dry age-related macular degeneration, or Usher syndrome.
13 . A method comprising administering the rAAV particle of claim 10 to a subject having a retinal disease, disorder or condition, wherein the disease, disorder or condition is retinitis pigmentosa, rod dystrophy, wet age-related macular degeneration, dry age-related macular degeneration, or Usher syndrome.
14 . The method of claim 13 , wherein expression of the transgene is at least 80% higher in rod cells than in cone cells of the subject.
15 . The method of claim 13 , wherein expression of the transgene is at least 90% higher in rod cells than in cone cells of the subject.
16 . A recombinant viral vector comprising a polynucleotide encoding a transgene operably linked to a promoter that has a nucleotide sequence consisting of SEQ ID NO: 16.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Dec 12, 2023
From: UNIVERSITY OF FLORIDA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065967/0491 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 22, 2021
From: DYKA, FRANK M.; HAUSWIRTH, WILLIAM W.
To: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED
Reel/Frame 058458/0691 →
Continuity (2)
Provisional Application
62813681
· Mar 4, 2019
References Cited (123)
US 5139941A
· Muzyczka et al.
· 1992
[cited by applicant]
US 5962313A
· Podsakoff et al.
· 1999
[cited by applicant]
US 20070015238A1
· Snyder et al.
· 2007
[cited by applicant]
US 20120093772A1
· Horsager et al.
· 2012
[cited by applicant]
US 20120322861A1
· Byrne et al.
· 2012
[cited by applicant]
US 20210130421A1
· Boye et al.
· 2021
[cited by applicant]
Detrick and Hooks, Immune regulation in the retina. Immunol Res (2010), 47: 153-161 (Year: 2010).
[cited by examiner]
Khanani et al., Review of gene therapies for age-related macular degeneration. Eye (2022), 36:303-311 (Year: 2022).
[cited by examiner]
Woodburn et al., Sight of Action: the Rationale and Evolution of Gene Therapy Approaches to the Treatment of Retinal Diseases. Current Ophthalmology Reports (2020) 8:267-280 (Year: 2020).
[cited by examiner]
Mandal et al., Nanoparticle-mediated gene therapy as a novel strategy for the treatment of retinoblastoma. Colloids and Surfaces B: Biointerfaces (2022), 112899 (Year: 2022).
[cited by examiner]
Lee et al., Quantitative fine-tuning of photoreceptor cis-regulatory elements through affinity modulation of transcription factor binding sites. Gene Therapy (2010), 17: 1390-1399, and Supplemental Material (Year: 2010).
[cited by examiner]
Dinculescu et al., Retinal gene therapy for Usher syndrome: current developments, challenges, and perspectives. International Ophthalmology Clinics (2021), 61:109-124 (Year: 2021).
[cited by examiner]
Rickman et al., Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging. Invest Ophthalmol Vis Sci. (2013), 54:ORSF68-ORSF80 (Year: 2013).
[cited by examiner]
Iannaccone et al., Kinetics of Visual Field Loss in Usher Syndrome Type II. Investigative Ophthalmology & Visual Science (2004), vol. 45, 784-792. (Year: 2004).
[cited by examiner]
Botta et al., Rhodopsin targeted transcriptional silencing by DNA-binding. eLife (2016), 5:e12242 pp. 1-14 (Year: 2016).
[cited by examiner]
NG_009115.1,
[cited by examiner]
Barbier et al., Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4a. Molecular Pharmacology (2005), 67: 241-249 (Year: 2005).
[cited by examiner]
Cheng et al., Transcriptomics-Guided Design of Synthetic Promoters for a Mammalian System. ACS Synthetic Biology (2016), 5: 1455-1465 (Year: 2016).
[cited by examiner]
Vandenberghe and Auricchio, Novel adeno-associated viral vectors for retinal gene therapy. Gene Therapy (2011), 19: 162-168 (Year: 2011).
[cited by examiner]
International Search Report and Written Opinion mailed Jun. 11, 2020 for Application No. PCT/US2020/020888.
[cited by applicant]
International Preliminary Report on Patentability mailed on Sep. 16, 2021 for Application No. PCT/US2020/020888.
[cited by applicant]
Allocca et al., Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors. J Virol. Oct. 2007;81(20):11372-80. doi: 10.1128/JVI.01327-07. Epub Aug. 15, 2007.
[cited by applicant]
Annear et al., Gene therapy in the second eye of RPE65-deficient dogs improves retinal function. Gene Ther. Jan. 2011;18(1):53-61. doi: 10.1038/gt.2010.111. Epub Aug. 12, 2010. Author Manuscript, 22 pages.
[cited by applicant]
Annear et al., Reproducibility of an objective four-choice canine vision testing technique that assesses vision at differing light intensities. Vet Ophthalmol. Sep. 2013;16(5):324-8. doi: 10.1111/j.1463-5224.2012.01076.…
[cited by applicant]
Annear et al., Successful gene therapy in older Rpe65-deficient dogs following subretinal injection of an adeno-associated vector expressing RPE65. Hum Gene Ther. Oct. 2013;24(10):883-93. doi: 10.1089/hum.2013.146.
[cited by applicant]
Asokan et al., The AAV vector toolkit: poised at the clinical crossroads. Mol Ther. Apr. 2012;20(4):699-708. doi: 10.1038/mt.2011.287. Epub Jan. 24, 2012.
[cited by applicant]
Auricchio et al., Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. Hum Mol Genet. Dec. 15, 2001;10(26):3075-81. doi: 10.1093/hmg/10.26.30…
[cited by applicant]
Azam et al., Identification of novel mutations in Pakistani families with autosomal recessive retinitis pigmentosa. Arch Ophthalmol. Oct. 2011;129(10):1377-8. doi: 10.1001/archophthalmol.2011.290.
[cited by applicant]
Bainbridge et al., Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. May 22, 2008;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub Apr. 27, 2008.
[cited by applicant]
Bainbridge et al., Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. May 14, 2015;372(20):1887-97. doi: 10.1056/NEJMoa1414221. Epub May 4, 2015.
[cited by applicant]
Bareil et al., 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. Apr. 2001;108(4):328-34. doi: 10.1007/s0043…
[cited by applicant]
Beltran et al., Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations. PLoS One. Mar. 5, 2014;9(3):e90390. doi: 10.1371/journal.pone.0090390.
[cited by applicant]
Beltran et al., Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci U S A. Feb. 7, 2012;109(6):2132-7. doi: 10.1073/pnas.1118847109…
[cited by applicant]
Bennett et al., AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. Feb. 8, 2012;4(120):120ra15. doi: 10.1126/scitranslmed.3002865. Author Manuscript, 24 pages.
[cited by applicant]
Biel et al., Function and dysfunction of CNG channels: insights from channelopathies and mouse models. Mol Neurobiol. Jun. 2007;35(3):266-77. doi: 10.1007/s12035-007-0025-y.
[cited by applicant]
Bocquet et al., Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations. Mol Vis. Dec. 8, 2013;19:2487-500.
[cited by applicant]
Boyd et al., Photoreceptor-targeted gene delivery using intravitreally administered AAV vectors in dogs. Gene Ther. Feb. 2016;23(2):223-30. doi: 10.1038/gt.2015.96. Epub Oct. 15, 2015. Erratum in: Gene Ther. Apr. 2016;2…
[cited by applicant]
Brutlag et al., Improved sensitivity of biological sequence database searches. Comput Appl Biosci. Jul. 1990;6(3):237-45. doi: 10.1093/bioinformatics/6.3.237.
[cited by applicant]
Cideciyan et al., Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. Feb. 5, 2013;110(6):E517-25. doi: 10.1073/p…
[cited by applicant]
Cideciyan et al., Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther. Sep. 2009;20(9):999-1004. doi: 10.1089/hum.2009.086.
[cited by applicant]
Cook et al., The cGMP-gated channel of bovine rod photoreceptors is localized exclusively in the plasma membrane. J Biol Chem. Apr. 25, 1989;264(12):6996-9.
[cited by applicant]
Daiger et al., Data services and software for identifying genes and mutations causing retinal degeneration. Invest Ophthalmol Vis Sci. Jan. 25, 1998;39:S295.
[cited by applicant]
Delori et al., In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. Mar. 1995;36(3):718-29.
[cited by applicant]
Desmet et al., Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. May 2009;37(9):e67. doi: 10.1093/nar/gkp215. Epub Apr. 1, 2009.
[cited by applicant]
Duan et al., Enhancement of muscle gene delivery with pseudotyped adeno-associated virus type 5 correlates with myoblast differentiation. J Virol. Aug. 2001;75(16):7662-71. doi: 10.1128/JVI.75.16.7662-7671.2001.
[cited by applicant]
Duncker et al., Comparison of near-infrared and short-wavelength autofluorescence in retinitis pigmentosa. Invest Ophthalmol Vis Sci. Jan. 17, 2013;54(1):585-91. doi: 10.1167/iovs.12-11176.
[cited by applicant]
Flannery et al., Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. Proc Natl Acad Sci U S A. Jun. 24, 1997;94(13):6916-21. doi: 10.1073/pnas.94.13.6916.
[cited by applicant]
Fradin et al., Run of homozygosity analysis reveals a novel nonsense variant of the CNGB1 gene involved in retinitis pigmentosa 45. Ophthalmic Genet. Sep. 2016;37(3):357-9. 10.3109/13816810.2015.1087578 . hal-01282329.
[cited by applicant]
Fu et al., Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci. Jun. 14, 2013;54(6):4158-66. doi: 10.1167/iovs.13-116…
[cited by applicant]
Gearhart et al., A novel method for objective vision testing in canine models of inherited retinal disease. Invest Ophthalmol Vis Sci. Aug. 2008;49(8):3568-76. doi: 10.1167/iovs.07-0625.
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NM_001284462.1, Canis lupus familiaris cyclic nucleotide gated channel beta 1 (CNGB1), mRNA, Feb. 25, 2018, https://www.ncbi.nlm.nih.gov/nuccore/548923831?sat=47&satkey=323178…
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NM_001286130.1,
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NM_001297.4,
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NP_001129111.1, cyclic nucleotide-gated cation channel beta-1 isoform b [
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NP_001273059, cyclic nucleotide-gated channel beta-1 isoform c [
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. NP_001288.3, cyclic nucleotide-gated cation channel beta-1 isoform a [
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. XM_011522870.2, Predicted:
[cited by applicant]
Genbank Submission; NIH/NCBI, Accession No. XP_011521172.1, cyclic nucleotide-gated cation channel beta-1 isoform X1 [
[cited by applicant]
Grimm et al., Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol Ther. Jun. 2003;7(6):839-50. doi: 10.1016/s1525-0016(03)00095-9.
[cited by applicant]
Grimm et al., Novel tools for production and purification of recombinant adenoassociated virus vectors. Hum Gene Ther. Dec. 10, 1998;9(18):2745-60. doi: 10.1089/hum.1998.9.18-2745.
[cited by applicant]
Halbert et al., Repeat transduction in the mouse lung by using adeno-associated virus vectors with different serotypes. J Virol. Feb. 2000;74(3):1524-32. doi: 10.1128/jvi.74.3.1524-1532.2000.
[cited by applicant]
Hartong et al., Retinitis pigmentosa. Lancet. Nov. 18, 2006;368(9549):1795-809. doi: 10.1016/S0140-6736(06)69740-7.
[cited by applicant]
Hauswirth et al., Production and purification of recombinant adeno-associated virus. Methods Enzymol. 2000;316:743-61. doi: 10.1016/s0076-6879(00)16760-6.
[cited by applicant]
Hauswirth et al., 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. Oct. 2008; 19(…
[cited by applicant]
Hood et al., Assessing abnormal rod photoreceptor activity with the a-wave of the electroretinogram: applications and methods. Doc Ophthalmol. 1996-1997;92(4):253-67. doi: 10.1007/BF02584080.
[cited by applicant]
Hood et al., Measuring the Health of the Human Photoreceptors with the Leading Edge of the a-Wave. Chapter 35. In: Heckenlively JR, Arden GB, eds. Principles and practice of clinical electrophysiology of Vision. Cambrid…
[cited by applicant]
Hood et al., Thickness of receptor and post-receptor retinal layers in patients with retinitis pigmentosa measured with frequency-domain optical coherence tomography. Invest Ophthalmol Vis Sci. May 2009;50(5):2328-36. d…
[cited by applicant]
Hull et al., Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa. JAMA Ophthalmol. Feb. 1, 2017;135(2):137-144. doi: 10.1001/jamaophthalmol.2016.5213.
[cited by applicant]
Hüttl et al., Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1. J Neurosci. Jan. 5, 2005;25(1):130-8. doi: 10.1523/JNEUROSCI.3764-04.2005.
[cited by applicant]
Kaupp et al., Cyclic nucleotide-gated ion channels. Physiol Rev. Jul. 2002;82(3):769-824. doi: 10.1152/physrev.00008.2002.
[cited by applicant]
Kern et al., Identification of a heparin-binding motif on adeno-associated virus type 2 capsids. J Virol. Oct. 2003;77(20):11072-81. doi: 10.1128/jvi.77.20.11072-11081.2003.
[cited by applicant]
Kessler et al., Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc Natl Acad Sci U S A. Nov. 26, 1996;93(24):14082-7. doi: 10.1073/pnas.93.24.14082.
[cited by applicant]
Khani et al., AAV-mediated expression targeting of rod and cone photoreceptors with a human rhodopsin kinase promoter. Invest Ophthalmol Vis Sci. Sep. 2007;48(9):3954-61. doi: 10.1167/iovs.07-0257.
[cited by applicant]
Koch et al., Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa. Hum Mol Genet. Oct. 15, 2012;21(20):4486-96. doi: 10.1093/hmg/dds290. Epub Jul. 16, 2012.
[cited by applicant]
Kondo et al., A homozygosity-based search for mutations in patients with autosomal recessive retinitis pigmentosa, using microsatellite markers. Invest Ophthalmol Vis Sci. Dec. 2004;45(12):4433-9. doi: 10.1167/iovs.04-0…
[cited by applicant]
Körschen et al., A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor. Neuron. Sep. 1995;15(3):627-36. doi: 10.1016/0896-6273(95)90151-5.
[cited by applicant]
Kronenberg et al., A conformational change in the adeno-associated virus type 2 capsid leads to the exposure of hidden VP1 N termini. J Virol. May 2005;79(9):5296-303. doi: 10.1128/JVI.79.9.5296-5303.2005.
[cited by applicant]
Li et al., Retinoic acid upregulates cone arrestin expression in retinoblastoma cells through a Cis element in the distal promoter region. Invest Ophthalmol Vis Sci. May 2002;43(5):1375-83.
[cited by applicant]
Lima et al., Progressive constriction of the hyperautofluorescent ring in retinitis pigmentosa. Am J Ophthalmol. Apr. 2012;153(4):718-27, 727.e1-2. doi: 10.1016/j.ajo.2011.08.043. Epub Dec. 3, 2011. Author Manuscript, 1…
[cited by applicant]
Lima et al., Structural assessment of hyperautofluorescent ring in patients with retinitis pigmentosa. Retina. Jul.-Aug. 2009;29(7):1025-31. doi: 10.1097/IAE.0b013e3181ac2418. Author Manuscript, 13 pages.
[cited by applicant]
MacLaren et al., Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. Mar. 29, 2014;383(9923):1129-37. doi: 10.1016/S0140- 6736(13)62117-0. Epub Jan. 16, 2014.
[cited by applicant]
Maguire et al., Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. May 22, 2008;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub Apr. 27, 2008.
[cited by applicant]
Maranhao et al., Investigating the Molecular Basis of Retinal Degeneration in a Familial Cohort of Pakistani Decent by Exome Sequencing. PLoS One. Sep. 9, 2015;10(9):e0136561. doi: 10.1371/journal.pone.0136561.
[cited by applicant]
Maria et al., Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan. PLoS One. Mar. 16, 2015;10(3):e0119806. doi: 10.1371/journal.pone.…
[cited by applicant]
McCulloch et al., ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol. Feb. 2015;130(1):1-12. doi: 10.1007/s10633-014-9473-7. Epub Dec. 14, 2014. Erratum in: Doc Ophthalmol. Aug. 201…
[cited by applicant]
Mears et al., Nrl is required for rod photoreceptor development. Nat Genet. Dec. 2001;29(4):447-52. doi: 10.1038/ng774.
[cited by applicant]
Mitton et al., The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. J Biol Chem. Sep. 22, 2000;275(38):29794-9. doi: 10.1074/jbc.M0036582…
[cited by applicant]
Moullier et al., International efforts for recombinant adeno-associated viral vector reference standards. Mol Ther. Jul. 2008;16(7):1185-8. doi: 10.1038/mt.2008.125.
[cited by applicant]
Mowat et al., RPE65 gene therapy slows cone loss in Rpe65-deficient dogs. Gene Ther. May 2013;20(5):545-55. doi: 10.1038/gt.2012.63. Epub Sep. 6, 2012.
[cited by applicant]
Nishiguchi et al., Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. Proc Natl Acad Sci U S A. Oct. 1, 2013;110(40):16139-44. doi: 10…
[cited by applicant]
Petersen-Jones et al., AAV retinal transduction in a large animal model species: comparison of a self-complementary AAV2/5 with a single-stranded AAV2/5 vector. Mol Vis. Sep. 11, 2009;15:1835-42.
[cited by applicant]
Provis et al., Adaptation of the central retina for high acuity vision: cones, the fovea and the avascular zone. Prog Retin Eye Res. Jul. 2013;35:63-81. doi: 10.1016/j.preteyeres.2013.01.005. Epub Mar. 15, 2013. Author …
[cited by applicant]
Remington's Pharmaceutical Sciences, 1975, 15th Edition, pp. 1035-1038 and 1570-1580.
[cited by applicant]
Robson et al., Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa. Retina. Sep. 2011;31(8):1670-9. doi: 10.1097/IAE.0b013e318206d155.
[cited by applicant]
Saqib et al., Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies. Sci Rep. May 6, 2015;5:9965. doi: 10.1038/srep09965.
[cited by applicant]
Schimmer et al., Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results. Hum Gene Ther Clin Dev. Dec. 2015;26(4):208-10. doi: 10.1089/humc.2015.29004.sch.
[cited by applicant]
Schnur et al., Phenotypic variability in X-linked ocular albinism: relationship to linkage genotypes. Am J Hum Genet. Sep. 1994;55(3):484-96.
[cited by applicant]
Schön et al., Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia. Hum Mol Genet. Mar. 15, 2016;25(6):1165-75. doi: 10.1093/hmg/ddv639. Epub Jan. 5, 201…
[cited by applicant]
Schorderet et al., IROme, a new high-throughput molecular tool for the diagnosis of inherited retinal dystrophies. Biomed Res Int. 2013;2013:198089. doi: 10.1155/2013/198089. Epub Dec. 26, 2012.
[cited by applicant]
Schuerch et al., Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. Mar. 1, 2017;58(3):1843-1855. doi: 10.1167/iovs.16-21302.
[cited by applicant]
Seeliger et al., New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis. Nat Genet. Sep. 2001;29(1):70-4. doi: 10.1038/ng712.
[cited by applicant]
Shuart et al., Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels. Nat Commun. Aug. 30, 2011;2:457. doi: 10.1038/ncomms1466.
[cited by applicant]
Simpson et al., Molecular diagnosis for heterogeneous genetic diseases with targeted high-throughput DNA sequencing applied to retinitis pigmentosa. J Med Genet. Mar. 2011;48(3):145-51. doi: 10.1136/jmg.2010.083568. Epu…
[cited by applicant]
Spaide et al., Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model. Retina. Sep. 2011;31(8):1609-19. doi: 10.1097/IAE.0b013e3182247535. Author Manuscr…
[cited by applicant]
Spurr, A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. Jan. 1969;26(1):31-43. doi: 10.1016/s0022-5320(69)90033-1.
[cited by applicant]
Staurenghi et al., Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN.OCT consensus. Ophthalmology. Aug. 2014;121(8):1572-8. doi: 10.1016/j.ophtha.20…
[cited by applicant]
Sujirakul et al., Multimodal Imaging of Central Retinal Disease Progression in a 2-Year Mean Follow-up of Retinitis Pigmentosa. Am J Ophthalmol. Oct. 2015;160(4):786-98.e4. doi: 10.1016/j.ajo.2015.06.032. Epub Jul. 9, 2…
[cited by applicant]
Tanimoto et al., Vision tests in the mouse: Functional phenotyping with electroretinography. Front Biosci (Landmark Ed). Jan. 1, 2009;14(7):2730-7. doi: 10.2741/3409.
[cited by applicant]
Tao et al., Ellipsoid zone on optical coherence tomography: a review. Clin Exp Ophthalmol. Jul. 2016;44(5):422-30. doi: 10.1111/ceo.12685. Epub Feb. 11, 2016.
[cited by applicant]
Thomas et al., Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity? Ophthalmology. Aug. 2011;118(8):1653-60. doi: 10.1016/j.ophtha.2011.01.028. Epub Ap…
[cited by applicant]
Tuntinavich et al., Characterization of a canine model of autosomal recessive retinitis pigmentosa due to a PDE6A mutation. Invest Ophthalmol Vis Sci. Feb. 2009;50(2):801-13. doi: 10.1167/iovs.08-2562. Epub Sep. 4, 2008…
[cited by applicant]
Weitzman et al., Targeted integration by adeno-associated virus. Methods Mol Med. 2003;76:201-19. doi: 10.1385/1-59259-304-6:201.
[cited by applicant]
Winkler et al., A large animal model for CNGB1 autosomal recessive retinitis pigmentosa. PLoS One. Aug. 19, 2013;8(8):e72229. doi: 10.1371/journal.pone.0072229.
[cited by applicant]
Zhang et al., Chemical chaperone TUDCA preserves cone photoreceptors in a mouse model of Leber congenital amaurosis. Invest Ophthalmol Vis Sci. Jun. 5, 2012;53(7):3349-56. doi: 10.1167/iovs.12-9851.
[cited by applicant]
Zhong et al., AAV8(Y733F)-mediated gene therapy in a Spata7 knockout mouse model of Leber congenital amaurosis and retinitis pigmentosa. Gene Ther. Aug. 2015;22(8):619-27. doi: 10.1038/gt.2015.42. Epub May 12, 2015. Aut…
[cited by applicant]
Zolotukhin et al., Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors. Methods. Oct. 2002;28(2):158-67. doi: 10.1016/s1046-2023(02)00220-7.
[cited by applicant]