Alfred S Lewin

Alfred S Lewin,

Professor Emeritus

Department: Molecular Genetics & Microbiology
Business Email: lewin@mgm.ufl.edu

About Alfred S Lewin

Dr. Lewin was born in Chicago, Illinois, USA and received B.A. and Ph.D. degrees in biology from the University of Chicago. Dr. Lewin’s postdoctoral training was in Basel, Switzerland. After establishing an independent research group in the Department of Chemistry at Indiana University, he was recruited to the University of Florida College of Medicine in 1987. Since 1994, he has working on gene therapy approaches for treatment of autosomal dominant retinitis pigmentosa. He is also collaborating on projects for treatment of X-linked retinitis pigmentosa and for therapy of age-related macular degeneration. Currently, Dr. Lewin is Shaler-Richardson Professor of Ophthalmic Sciences and is Professor of Molecular Genetics and Microbiology at the University of Florida.

Related Links:

Teaching Profile

Courses Taught
2016,2020-2021
GMS6251 Molecular Therapy I ? Vectors and Molecular Mechanisms
2018
GMS7980 Research for Doctoral Dissertation
2018
GMS7979 Advanced Research
2015,2017-2018
GMS5905 Special Topics in Biomedical Sciences
2013-2016
BCH7410 Advanced Gene Regulation
2013,2015
GMS6709 Current Topics in Vision
2013-2014,2021
GMS6622 Mitochondrial Biology in Aging and Disease
2009
IDH4917 Undergrad Research

Research Profile

My laboratory is developing both gene and pharmacologic therapies for diseases of the retina and optic nerve. These disease include autosomal dominant retinitis pigmentosa (adRP), X-linked retinitis pigmentosa (xlRP), Leber Hereditary Optic Neuropathy (LHON), age related macular degeneration (AMD), and uveitis. For example, in collaboration with investigators at the University of Pennsylvania, we tested gene therapy for adRP and xlRP in canine models of these diseases in preparation for clinical testing in human patients. In partnership with Dr. John Guy at the University of Miami, we have developed two different gene therapies for the mitochondrial disease Leber Hereditary Optic Neuropathy. A motivation of current research is to develop a gene therapy approach for the treatment of advanced dry age related macular degeneration (AMD). My group’s efforts have been focused on developing a mouse model that recapitulates some of the features of this disease, as closely as possible in an animal without a macula. We have tested the hypothesis that mitochondrial oxidative stress in the retinal pigment epithelium (RPE) contributes to RPE dysfunction and death, leading to localized retinal atrophy. In this model, we have tested both drug gene therapy vectors to block inflammation arising from oxidative stress. We have also used both gene therapy and topically delivered peptide for the treatment of the ocular inflammation known as uveitis. These approaches have proven extremely effective in models of autoimmune uveitis and infectious uveitis.

Open Researcher and Contributor ID (ORCID)

0000-0002-4192-9727

Publications

2022
Gene Delivery of a Caspase Activation and Recruitment Domain Improves Retinal Pigment Epithelial Function and Modulates Inflammation in a Mouse Model with Features of Dry Age-Related Macular Degeneration.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 38(5):359-371 [DOI] 10.1089/jop.2022.0002. [PMID] 35446130.
2022
Gene Therapy for Rhodopsin Mutations
Cold Spring Harbor Perspectives in Medicine. 12(9) [DOI] 10.1101/cshperspect.a041283. [PMID] 35940643.
2022
Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides.
Frontiers in immunology. 13 [DOI] 10.3389/fimmu.2022.902956. [PMID] 35799776.
2021
Automated segmentation and analysis of retinal microglia within ImageJ
Experimental Eye Research. 203 [DOI] 10.1016/j.exer.2020.108416. [PMID] 33359513.
2021
Corneal Application of R9-SOCS1-KIR Peptide Alleviates Endotoxin-Induced Uveitis.
Translational vision science & technology. 10(3) [DOI] 10.1167/tvst.10.3.25. [PMID] 34003962.
2021
Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium.
Antioxidants (Basel, Switzerland). 10(6) [DOI] 10.3390/antiox10060842. [PMID] 34070383.
2021
Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.
International ophthalmology clinics. 61(4):79-96 [DOI] 10.1097/IIO.0000000000000383. [PMID] 34584046.
2020
A C-terminal peptide from type I interferon protects the retina in a mouse model of autoimmune uveitis
PLOS ONE. 15(2) [DOI] 10.1371/journal.pone.0227524. [PMID] 32101556.
2020
Sectoral activation of glia in an inducible mouse model of autosomal dominant retinitis pigmentosa.
Scientific reports. 10(1) [DOI] 10.1038/s41598-020-73749-y. [PMID] 33046772.
2020
SOCS, Intrinsic Virulence Factors, and Treatment of COVID-19.
Frontiers in immunology. 11 [DOI] 10.3389/fimmu.2020.582102. [PMID] 33193390.
2019
AAV Mediated Delivery of Myxoma Virus M013 Gene Protects the Retina against Autoimmune Uveitis
Journal of Clinical Medicine. 8(12) [DOI] 10.3390/jcm8122082. [PMID] 31795515.
2019
AMPK May Play an Important Role in the Retinal Metabolic Ecosystem.
Advances in experimental medicine and biology. 1185:477-481 [DOI] 10.1007/978-3-030-27378-1_78. [PMID] 31884657.
2019
Biodistribution of adeno-associated virus type 2 with mutations in the capsid that contribute to heparan sulfate proteoglycan binding.
Virus research. 274 [DOI] 10.1016/j.virusres.2019.197771. [PMID] 31577935.
2019
Co-Delivery of a Short-Hairpin RNA and a shRNA-Resistant Replacement Gene with Adeno-Associated Virus: An Allele-Independent Strategy for Autosomal-Dominant Retinal Disorders.
Methods in molecular biology (Clifton, N.J.). 1937:235-258 [DOI] 10.1007/978-1-4939-9065-8_15. [PMID] 30706401.
2019
Expression of a CARD Slows the Retinal Degeneration of a Geographic Atrophy Mouse Model.
Molecular therapy. Methods & clinical development. 14:113-125 [DOI] 10.1016/j.omtm.2019.06.001. [PMID] 31334304.
2019
Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors.
Redox biology. 24 [DOI] 10.1016/j.redox.2019.101201. [PMID] 31039480.
2019
Myxoma virus M013 protein antagonizes NF-κB and inflammasome pathways via distinct structural motifs
Journal of Biological Chemistry. 294(21):8480-8489 [DOI] 10.1074/jbc.ra118.006040.
2019
Myxoma virus M013 protein antagonizes NF-κB and inflammasome pathways via distinct structural motifs
Journal of Biological Chemistry. 294(21):8480-8489 [DOI] 10.1074/jbc.ra118.006040.
2019
Preface.
Current gene therapy. 19(1) [DOI] 10.2174/156652321901190502112219. [PMID] 31190638.
2019
SRD005825 Acts as a Pharmacologic Chaperone of Opsin and Promotes Survival of Photoreceptors in an Animal Model of Autosomal Dominant Retinitis Pigmentosa.
Translational vision science & technology. 8(6) [DOI] 10.1167/tvst.8.6.30. [PMID] 31857914.
2018
A cell penetrating peptide from SOCS-1 prevents ocular damage in experimental autoimmune uveitis
Experimental Eye Research. 177:12-22 [DOI] 10.1016/j.exer.2018.07.020. [PMID] 30048621.
2018
Adeno-Associated Virus Delivery of Viral Serpins for Ocular Diseases: Design and Validation.
Methods in molecular biology (Clifton, N.J.). 1826:237-254 [DOI] 10.1007/978-1-4939-8645-3_16. [PMID] 30194605.
2018
Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization.
Journal of molecular medicine (Berlin, Germany). 96(10):1107-1118 [DOI] 10.1007/s00109-018-1683-0. [PMID] 30105447.
2018
Clinically Relevant Outcome Measures for the I307N Rhodopsin Mouse: A Model of Inducible Autosomal Dominant Retinitis Pigmentosa.
Investigative ophthalmology & visual science. 59(13):5417-5430 [DOI] 10.1167/iovs.18-25345. [PMID] 30452595.
2018
Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress.
PloS one. 13(9) [DOI] 10.1371/journal.pone.0203816. [PMID] 30265681.
2018
Delivery of CR2-fH Using AAV Vector Therapy as Treatment Strategy in the Mouse Model of Choroidal Neovascularization.
Molecular therapy. Methods & clinical development. 9:1-11 [DOI] 10.1016/j.omtm.2017.11.003. [PMID] 29234687.
2018
In Vivo Knockdown of the Herpes Simplex Virus 1 Latency-Associated Transcript Reduces Reactivation from Latency.
Journal of virology. 92(16) [DOI] 10.1128/JVI.00812-18. [PMID] 29875240.
2018
Longterm Reversal of Severe Visual Loss by Mitochondrial Gene Transfer in a Mouse Model of Leber Hereditary Optic Neuropathy.
Scientific reports. 8(1) [DOI] 10.1038/s41598-018-23836-y. [PMID] 29615737.
2018
Mitochondria: Potential Targets for Protection in Age-Related Macular Degeneration.
Advances in experimental medicine and biology. 1074:11-17 [DOI] 10.1007/978-3-319-75402-4_2. [PMID] 29721922.
2018
Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector
Proceedings of the National Academy of Sciences. 115(36) [DOI] 10.1073/pnas.1805055115. [PMID] 30127005.
2018
Neuroinflammation in Retinitis Pigmentosa, Diabetic Retinopathy, and Age-Related Macular Degeneration: A Minireview.
Advances in experimental medicine and biology. 1074:185-191 [DOI] 10.1007/978-3-319-75402-4_23. [PMID] 29721943.
2018
Preface: Translational Gene Therapy Coming of Age!
Current gene therapy. 18(1) [DOI] 10.2174/156652321801180503163908. [PMID] 29769000.
2017
Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.
PloS one. 12(2) [DOI] 10.1371/journal.pone.0171940. [PMID] 28222108.
2017
Systemic Injection of RPE65-Programmed Bone Marrow-Derived Cells Prevents Progression of Chronic Retinal Degeneration.
Molecular therapy : the journal of the American Society of Gene Therapy. 25(4):917-927 [DOI] 10.1016/j.ymthe.2017.01.015. [PMID] 28202390.
2017
Timing of Antioxidant Gene Therapy: Implications for Treating Dry AMD.
Investigative ophthalmology & visual science. 58(2):1237-1245 [DOI] 10.1167/iovs.16-21272. [PMID] 28241311.
2016
Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.
Advances in experimental medicine and biology. 854:185-91 [DOI] 10.1007/978-3-319-17121-0_25. [PMID] 26427410.
2016
Adeno-associated Virus Vectors Efficiently Transduce Mouse and Rabbit Sensory Neurons Coinfected with Herpes Simplex Virus 1 following Peripheral Inoculation.
Journal of virology. 90(17):7894-901 [DOI] 10.1128/JVI.01028-16. [PMID] 27334582.
2016
Characterization of Ribozymes Targeting a Congenital Night Blindness Mutation in Rhodopsin Mutation.
Advances in experimental medicine and biology. 854:509-15 [DOI] 10.1007/978-3-319-17121-0_68. [PMID] 26427453.
2016
Conditional Induction of Oxidative Stress in RPE: A Mouse Model of Progressive Retinal Degeneration.
Advances in experimental medicine and biology. 854:31-7 [DOI] 10.1007/978-3-319-17121-0_5. [PMID] 26427390.
2016
Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.
PloS one. 11(6) [DOI] 10.1371/journal.pone.0157411. [PMID] 27299810.
2016
MRI of Retinal Free Radical Production With Laminar Resolution In Vivo.
Investigative ophthalmology & visual science. 57(2):577-85 [DOI] 10.1167/iovs.15-18972. [PMID] 26886890.
2016
Repurposing an orally available drug for the treatment of geographic atrophy.
Molecular vision. 22:294-310 [PMID] 27110092.
2016
Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide.
Investigative ophthalmology & visual science. 57(2):372-86 [DOI] 10.1167/iovs.15-17703. [PMID] 26842755.
2016
The NLRP3 Inflammasome and its Role in Age-Related Macular Degeneration.
Advances in experimental medicine and biology. 854:59-65 [DOI] 10.1007/978-3-319-17121-0_9. [PMID] 26427394.
2015
Consequences of zygote injection and germline transfer of mutant human mitochondrial DNA in mice
Proceedings of the National Academy of Sciences. 112(42) [DOI] 10.1073/pnas.1506129112. [PMID] 26438859.
2015
Endurance training ameliorates complex 3 deficiency in a mouse model of Barth syndrome.
Journal of inherited metabolic disease. 38(5):915-22 [DOI] 10.1007/s10545-015-9834-8. [PMID] 25860817.
2015
Gene delivery of a viral anti-inflammatory protein to combat ocular inflammation.
Human gene therapy. 26(1):59-68 [DOI] 10.1089/hum.2014.089. [PMID] 25420215.
2015
Gene therapy to rescue retinal degeneration caused by mutations in rhodopsin.
Methods in molecular biology (Clifton, N.J.). 1271:391-410 [DOI] 10.1007/978-1-4939-2330-4_25. [PMID] 25697537.
2015
Gene therapy with the caspase activation and recruitment domain reduces the ocular inflammatory response.
Molecular therapy : the journal of the American Society of Gene Therapy. 23(5):875-884 [DOI] 10.1038/mt.2015.30. [PMID] 25698151.
2015
Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease
Proceedings of the National Academy of Sciences. 112(43) [DOI] 10.1073/pnas.1509914112. [PMID] 26460017.
2015
Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress
Experimental Eye Research. 140:94-105 [DOI] 10.1016/j.exer.2015.07.022. [PMID] 26315784.
2014
Assessment of anti-scarring therapies in ex vivo organ cultured rabbit corneas.
Experimental eye research. 125:173-82 [DOI] 10.1016/j.exer.2014.06.014. [PMID] 24971495.
2014
Drug and gene delivery to the back of the eye: from bench to bedside.
Investigative ophthalmology & visual science. 55(4):2714-30 [DOI] 10.1167/iovs.13-13707. [PMID] 24777644.
2014
Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.
Autophagy. 10(11):1989-2005 [DOI] 10.4161/auto.36184. [PMID] 25484094.
2014
Gene augmentation for adRP mutations in RHO.
Cold Spring Harbor perspectives in medicine. 4(9) [DOI] 10.1101/cshperspect.a017400. [PMID] 25037104.
2014
Gene augmentation for X-linked retinitis pigmentosa caused by mutations in RPGR.
Cold Spring Harbor perspectives in medicine. 5(2) [DOI] 10.1101/cshperspect.a017392. [PMID] 25301933.
2014
LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile.
Investigative ophthalmology & visual science. 55(12):7739-53 [DOI] 10.1167/iovs.14-15388. [PMID] 25342621.
2014
Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration.
Investigative ophthalmology & visual science. 55(7):4613-27 [DOI] 10.1167/iovs.14-14633. [PMID] 24985474.
2014
Modulation of the rate of retinal degeneration in T17M RHO mice by reprogramming the unfolded protein response.
Advances in experimental medicine and biology. 801:455-62 [DOI] 10.1007/978-1-4614-3209-8_58. [PMID] 24664731.
2014
Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.
JAMA ophthalmology. 132(4):409-20 [DOI] 10.1001/jamaophthalmol.2013.7630. [PMID] 24457989.
2013
A comprehensive review of retinal gene therapy.
Molecular therapy : the journal of the American Society of Gene Therapy. 21(3):509-19 [DOI] 10.1038/mt.2012.280. [PMID] 23358189.
2013
Ablation of C/EBP homologous protein does not protect T17M RHO mice from retinal degeneration.
PloS one. 8(4) [DOI] 10.1371/journal.pone.0063205. [PMID] 23646198.
2013
In vitro and in vivo characterization of a tunable dual-reactivity probe of the Nrf2-ARE pathway.
ACS chemical biology. 8(8):1764-74 [DOI] 10.1021/cb4000103. [PMID] 23773140.
2013
NADH-dehydrogenase type-2 suppresses irreversible visual loss and neurodegeneration in the EAE animal model of MS.
Molecular therapy : the journal of the American Society of Gene Therapy. 21(10):1876-88 [DOI] 10.1038/mt.2013.104. [PMID] 23752309.
2013
Triple combination of siRNAs targeting TGFβ1, TGFβR2, and CTGF enhances reduction of collagen I and smooth muscle actin in corneal fibroblasts.
Investigative ophthalmology & visual science. 54(13):8214-23 [DOI] 10.1167/iovs.13-12758. [PMID] 24282226.
2012
ACE2 and Ang-(1-7) confer protection against development of diabetic retinopathy.
Molecular therapy : the journal of the American Society of Gene Therapy. 20(1):28-36 [DOI] 10.1038/mt.2011.155. [PMID] 21792177.
2012
Functional rescue of P23H rhodopsin photoreceptors by gene delivery.
Advances in experimental medicine and biology. 723:191-7 [DOI] 10.1007/978-1-4614-0631-0_26. [PMID] 22183333.
2012
Gene delivery of wild-type rhodopsin rescues retinal function in an autosomal dominant retinitis pigmentosa mouse model.
Advances in experimental medicine and biology. 723:199-205 [DOI] 10.1007/978-1-4614-0631-0_27. [PMID] 22183334.
2012
Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber’s hereditary optic neuropathy in a mouse model.
Proceedings of the National Academy of Sciences of the United States of America. 109(20):E1238-47 [DOI] 10.1073/pnas.1119577109. [PMID] 22523243.
2012
Gene therapy in animal models of autosomal dominant retinitis pigmentosa.
Molecular vision. 18:2479-96 [PMID] 23077406.
2012
Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.
Proceedings of the National Academy of Sciences of the United States of America. 109(6):2132-7 [DOI] 10.1073/pnas.1118847109. [PMID] 22308428.
2012
Glucose regulated protein 78 diminishes α-synuclein neurotoxicity in a rat model of Parkinson disease.
Molecular therapy : the journal of the American Society of Gene Therapy. 20(7):1327-37 [DOI] 10.1038/mt.2012.28. [PMID] 22434142.
2012
Hammerhead ribozyme-mediated knockdown of mRNA for fibrotic growth factors: transforming growth factor-beta 1 and connective tissue growth factor.
Methods in molecular biology (Clifton, N.J.). 820:117-32 [DOI] 10.1007/978-1-61779-439-1_8. [PMID] 22131029.
2012
Long-Term Rescue By Aav-Delivered Therapy in Autosomal Dominant Retinitis Pigmentosa (Adrp) Mice
Molecular Therapy. 20
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.
Human gene therapy. 23(4):356-66 [DOI] 10.1089/hum.2011.213. [PMID] 22289036.
2012
Mutant NADH dehydrogenase subunit 4 gene delivery to mitochondria by targeting sequence-modified adeno-associated virus induces visual loss and optic atrophy in mice.
Molecular vision. 18:1668-83 [PMID] 22773905.
2012
Pathological consequences of long-term mitochondrial oxidative stress in the mouse retinal pigment epithelium.
Experimental eye research. 101:60-71 [DOI] 10.1016/j.exer.2012.05.013. [PMID] 22687918.
2012
Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.
Investigative ophthalmology & visual science. 53(13):8093-103 [DOI] 10.1167/iovs.12-10419. [PMID] 23139278.
2012
Suppression of rds expression by siRNA and gene replacement strategies for gene therapy using rAAV vector.
Advances in experimental medicine and biology. 723:215-23 [DOI] 10.1007/978-1-4614-0631-0_29. [PMID] 22183336.
2012
The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium.
PloS one. 7(4) [DOI] 10.1371/journal.pone.0034468. [PMID] 22509307.
2011
AAV delivery of wild-type rhodopsin preserves retinal function in a mouse model of autosomal dominant retinitis pigmentosa.
Human gene therapy. 22(5):567-75 [DOI] 10.1089/hum.2010.140. [PMID] 21126223.
2011
Characterization of a transgenic short hairpin RNA-induced murine model of Tafazzin deficiency.
Human gene therapy. 22(7):865-71 [DOI] 10.1089/hum.2010.199. [PMID] 21091282.
2011
Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina.
Molecular therapy : the journal of the American Society of Gene Therapy. 19(2):293-301 [DOI] 10.1038/mt.2010.234. [PMID] 21045809.
2011
Raav1 Vector-Mediated Expression of Tafazzin in Patient Fibroblasts and Murine Model of Barth Syndrome
Molecular Therapy. 19
2010
In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration.
Molecular therapy : the journal of the American Society of Gene Therapy. 18(8):1450-7 [DOI] 10.1038/mt.2010.115. [PMID] 20551914.
2010
rAAV2/5 gene-targeting to rods:dose-dependent efficiency and complications associated with different promoters.
Gene therapy. 17(9):1162-74 [DOI] 10.1038/gt.2010.56. [PMID] 20428215.
2010
Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78.
Proceedings of the National Academy of Sciences of the United States of America. 107(13):5961-6 [DOI] 10.1073/pnas.0911991107. [PMID] 20231467.
2010
The importance of mitochondria in age-related and inherited eye disorders.
Ophthalmic research. 44(3):179-90 [DOI] 10.1159/000316480. [PMID] 20829642.
2009
Delivery of antioxidant enzyme genes to protect against ischemia/reperfusion-induced injury to retinal microvasculature.
Investigative ophthalmology & visual science. 50(12):5587-95 [DOI] 10.1167/iovs.09-3633. [PMID] 19628743.
2009
Delivery of Antioxidant Genes Protects Retinal Microvasculature From Ischemia/Reperfusion Injury
Molecular Therapy. 17
2009
Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I subunit in the mouse visual system.
Investigative ophthalmology & visual science. 50(9):4205-14 [DOI] 10.1167/iovs.08-3214. [PMID] 19387075.
2009
Geographic atrophy in age-related macular degeneration and TLR3.
The New England journal of medicine. 360(21):2251; author reply 2255-6 [DOI] 10.1056/NEJMc082233. [PMID] 19458376.
2009
High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors.
Molecular therapy : the journal of the American Society of Gene Therapy. 17(3):463-71 [DOI] 10.1038/mt.2008.269. [PMID] 19066593.
2009
Suppression of Rds Expression By Sirna and Gene Replacement Strategies for Gene Therapy Using Aav Vector
Molecular Therapy. 17
2009
Tight Long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector.
Molecular therapy : the journal of the American Society of Gene Therapy. 17(11):1857-67 [DOI] 10.1038/mt.2009.196. [PMID] 19707186.
2008
Aav-Mediated Gene Transfer of Ace2 Protects Retinal Vascular Dysfunction in An Animal Model of Diabetic Retinopathy
Journal of Hypertension. 26
2008
AAV-mediated knockdown of phospholamban leads to improved contractility and calcium handling in cardiomyocytes.
The journal of gene medicine. 10(2):132-42 [PMID] 18064719.
2008
Different tropism of adenoviruses and adeno-associated viruses to corneal cells: implications for corneal gene therapy.
Molecular vision. 14:2087-96 [PMID] 19023450.
2008
Downregulation of p22phox in retinal pigment epithelial cells inhibits choroidal neovascularization in mice.
Molecular therapy : the journal of the American Society of Gene Therapy. 16(10):1688-94 [DOI] 10.1038/mt.2008.164. [PMID] 18665154.
2008
Effects of Raav Delivered Heat Shock Protein 27 and 70 To the Striatum of a Knock-in Mouse Model of Huntington’S Disease
Cell Transplantation. 17
2008
Gene therapy for mouse models of ADRP.
Advances in experimental medicine and biology. 613:107-12 [DOI] 10.1007/978-0-387-74904-4_11. [PMID] 18188934.
2008
In vitro analysis of ribozyme-mediated knockdown of an ADRP associated rhodopsin mutation.
Advances in experimental medicine and biology. 613:97-106 [DOI] 10.1007/978-0-387-74904-4_10. [PMID] 18188933.
2008
Reduction in severity of a herpes simplex virus type 1 murine infection by treatment with a ribozyme targeting the UL20 gene RNA.
Journal of virology. 82(15):7467-74 [DOI] 10.1128/JVI.02720-07. [PMID] 18508896.
2008
Unexpected off-targeting effects of anti-huntingtin ribozymes and siRNA in vivo.
Neurobiology of disease. 29(3):446-55 [DOI] 10.1016/j.nbd.2007.11.003. [PMID] 18166484.
2007
Anti-clarin-1 AAV-delivered ribozyme induced apoptosis in the mouse cochlea.
Hearing research. 230(1-2):9-16 [PMID] 17493778.
2007
Down-regulation of expression of rat pyruvate dehydrogenase E1alpha gene by self-complementary adeno-associated virus-mediated small interfering RNA delivery.
Mitochondrion. 7(4):253-9 [PMID] 17392036.
2007
Increased sensitivity to light-induced damage in a mouse model of autosomal dominant retinal disease.
Investigative ophthalmology & visual science. 48(5):1942-51 [PMID] 17460245.
2007
Long-term suppression of neurodegeneration in chronic experimental optic neuritis: antioxidant gene therapy.
Investigative ophthalmology & visual science. 48(12):5360-70 [PMID] 18055782.
2007
Preservation of photoreceptor morphology and function in P23H rats using an allele independent ribozyme.
Experimental eye research. 84(1):44-52 [PMID] 17083931.
2007
rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson’s disease.
Experimental neurology. 207(2):289-301 [PMID] 17678648.
2007
Rapid, widespread transduction of the murine myocardium using self-complementary Adeno-associated virus.
Genetic vaccines and therapy. 5 [PMID] 18070352.
2007
SOD2 knockdown mouse model of early AMD.
Investigative ophthalmology & visual science. 48(10):4407-20 [PMID] 17898259.
2007
Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis.
Investigative ophthalmology & visual science. 48(2):681-91 [PMID] 17251466.
2007
Suppression of mouse rhodopsin expression in vivo by AAV mediated siRNA delivery.
Vision research. 47(9):1202-8 [PMID] 17292939.
2007
The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse.
Investigative ophthalmology & visual science. 48(1):1-10 [PMID] 17197509.
2007
Use of mitochondrial antioxidant defenses for rescue of cells with a Leber hereditary optic neuropathy-causing mutation.
Archives of ophthalmology (Chicago, Ill. : 1960). 125(2):268-72 [PMID] 17296905.
2006
Down-regulation of rhodopsin gene expression by AAV-vectored short interfering RNA.
Advances in experimental medicine and biology. 572:233-8 [PMID] 17249579.
2006
Mitochondrial protein nitration primes neurodegeneration in experimental autoimmune encephalomyelitis.
The Journal of biological chemistry. 281(42):31950-62 [PMID] 16920708.
2006
RNA knockdown as a potential therapeutic strategy in Parkinson’s disease.
Gene therapy. 13(6):517-24 [PMID] 16267570.
2005
Gene therapy for autosomal dominant disorders of keratin.
The journal of investigative dermatology. Symposium proceedings. 10(1):47-61 [PMID] 16250209.
2005
Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington’s disease transgenic mice.
Molecular therapy : the journal of the American Society of Gene Therapy. 12(4):618-33 [PMID] 16019264.
2005
Knockdown of wild-type mouse rhodopsin using an AAV vectored ribozyme as part of an RNA replacement approach.
Molecular vision. 11:648-56 [PMID] 16145542.
2005
Ribozyme knockdown of the gamma-subunit of rod cGMP phosphodiesterase alters the ERG and retinal morphology in wild-type mice.
Investigative ophthalmology & visual science. 46(10):3836-44 [PMID] 16186371.
2004
Design and validation of therapeutic hammerhead ribozymes for autosomal dominant diseases.
Methods in molecular biology (Clifton, N.J.). 252:221-36 [PMID] 15017052.
2004
Hammerhead ribozyme targeting connective tissue growth factor mRNA blocks transforming growth factor-beta mediated cell proliferation.
Experimental eye research. 78(6):1127-36 [PMID] 15109919.
2004
Range of retinal diseases potentially treatable by AAV-vectored gene therapy.
Novartis Foundation symposium. 255:179-88; discussion 188 [PMID] 14750604.
2004
SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I.
Annals of neurology. 56(2):182-91 [PMID] 15293270.
2003
Decreased expression of the insulin-like growth factor 1 receptor by ribozyme cleavage.
Investigative ophthalmology & visual science. 44(9):4105-13 [PMID] 12939334.
2003
Identification of Candida albicans genes induced during thrush offers insight into pathogenesis.
Molecular microbiology. 48(5):1275-88 [PMID] 12787355.
2003
Optic neuropathy induced by reductions in mitochondrial superoxide dismutase.
Investigative ophthalmology & visual science. 44(3):1088-96 [PMID] 12601034.
2003
Reduction in preretinal neovascularization by ribozymes that cleave the A2B adenosine receptor mRNA.
Circulation research. 93(6):500-6 [PMID] 12919950.
2003
Suppression of complex I gene expression induces optic neuropathy.
Annals of neurology. 53(2):198-205 [PMID] 12557286.
2002
Designing and characterizing hammerhead ribozymes for use in AAV vector-mediated retinal gene therapies.
Methods in enzymology. 346:358-77 [PMID] 11883079.
2002
Development of hammerhead ribozymes to modulate endogenous gene expression for functional studies.
Methods (San Diego, Calif.). 28(2):276-85 [PMID] 12413427.
2002
Rescue of a mitochondrial deficiency causing Leber Hereditary Optic Neuropathy.
Annals of neurology. 52(5):534-42 [PMID] 12402249.
2001
An allele-specific hammerhead ribozyme gene therapy for a porcine model of autosomal dominant retinitis pigmentosa.
Molecular vision. 7:6-13 [PMID] 11172137.
2001
Inhibition of gene expression by ribozymes.
Methods in molecular medicine. 47:105-24 [DOI] 10.1385/1-59259-085-3:105. [PMID] 21394581.
2001
Noninvasive imaging by optical coherence tomography to monitor retinal degeneration in the mouse.
Investigative ophthalmology & visual science. 42(12):2981-9 [PMID] 11687546.
2001
Ribozyme gene therapy: applications for molecular medicine.
Trends in molecular medicine. 7(5):221-8 [PMID] 11325634.
2000
Production and purification of recombinant adeno-associated virus.
Methods in enzymology. 316:743-61 [PMID] 10800712.
2000
Ribozyme gene therapy for autosomal dominant retinal disease.
Clinical chemistry and laboratory medicine. 38(2):147-53 [PMID] 10834402.
2000
Ribozyme rescue of photoreceptor cells in P23H transgenic rats: long-term survival and late-stage therapy.
Proceedings of the National Academy of Sciences of the United States of America. 97(21):11488-93 [PMID] 11005848.
2000
Ribozyme uses in retinal gene therapy.
Progress in retinal and eye research. 19(6):689-710 [PMID] 11029552.
2000
Ribozymes in treatment of inherited retinal disease.
Methods in enzymology. 316:761-76 [PMID] 10800713.
1999
An RNA binding motif in the Cbp2 protein required for protein-stimulated RNA catalysis.
The Journal of biological chemistry. 274(43):30393-401 [PMID] 10521416.
1998
Inhibition of RNA synthesis as a therapeutic strategy against Aspergillus and Fusarium: demonstration of in vitro synergy between rifabutin and amphotericin B.
Antimicrobial agents and chemotherapy. 42(3):509-13 [PMID] 9517924.
1998
Ribozyme rescue of photoreceptor cells in a transgenic rat model of autosomal dominant retinitis pigmentosa.
Nature medicine. 4(8):967-71 [PMID] 9701253.
1998
Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis pigmentosa.
Investigative ophthalmology & visual science. 39(5):681-9 [PMID] 9538873.
1998
Selective degradation of nonsense beta-phosphodiesterase mRNA in the heterozygous rd mouse.
Investigative ophthalmology & visual science. 39(13):2529-36 [PMID] 9856762.
1997
Potentiation of antifungal activity of amphotericin B by azithromycin against Aspergillus species.
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 16(11):846-8 [PMID] 9447909.
1997
The Cbp2 protein stimulates the splicing of the omega intron of yeast mitochondria.
Nucleic acids research. 25(8):1597-604 [PMID] 9092668.
1996
The Cbp2 protein suppresses splice site mutations in a group I intron.
Nucleic acids research. 24(17):3415-23 [PMID] 8811097.
1995
Cotranscriptional splicing of a group I intron is facilitated by the Cbp2 protein.
Molecular and cellular biology. 15(12):6971-8 [PMID] 8524264.
1995
Protein-induced folding of a group I intron in cytochrome b pre-mRNA.
The Journal of biological chemistry. 270(37):21552-62 [PMID] 7665568.
1993
Selective autophagy of peroxisomes in methylotrophic yeasts.
European journal of cell biology. 60(2):283-90 [PMID] 8330626.
1992
A negative regulating element controlling transcription of the gene encoding acyl-CoA oxidase in Saccharomyces cerevisiae.
Nucleic acids research. 20(13):3495-500 [PMID] 1630920.
1992
Alternative topogenic signals in peroxisomal citrate synthase of Saccharomyces cerevisiae.
Molecular and cellular biology. 12(12):5593-9 [PMID] 1448089.
1992
Mutational evidence for competition between the P1 and the P10 helices of a mitochondrial group I intron.
Nucleic acids research. 20(9):2349-53 [PMID] 1375737.
1991
The rate and specificity of a group I ribozyme are inversely affected by choice of monovalent salt.
Nucleic acids research. 19(3):605-9 [PMID] 2011532.
1990
Citrate synthase encoded by the CIT2 gene of Saccharomyces cerevisiae is peroxisomal.
Molecular and cellular biology. 10(4):1399-405 [PMID] 2181273.
1990
Protein targeting to peroxisomes.
Biochemical Society transactions. 18(1):85-7 [PMID] 2185098.
1990
Splicing of COB intron 5 requires pairing between the internal guide sequence and both flanking exons.
Proceedings of the National Academy of Sciences of the United States of America. 87(21):8192-6 [PMID] 2236031.
1988
Autocatalytic activities of intron 5 of the cob gene of yeast mitochondria.
Molecular and cellular biology. 8(6):2562-71 [PMID] 3043183.
A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis
. [DOI] 10.1101/2019.12.23.886986.
Binocular Benefit Following Monocular Subretinal AAV Injection in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa (adRP)
. [DOI] 10.1101/2021.07.22.453413.

Grants

Aug 2019 – Jul 2021
mTORC1-TFEB Pathway in Degeneration of the RPE
Role: Principal Investigator
Funding: UNIV OF OKLAHOMA BOARD OF REGENTS via NATL INST OF HLTH NEI
Jan 2019 – Jan 2020
Production of AAV-RHO820-shRNA820
Role: Principal Investigator
Funding: IVERIC BIO
Jun 2018 – Jun 2019
Gene Therapy for RHO adRP
Role: Principal Investigator
Funding: IVERIC BIO
Sep 2017 – Jun 2019
The Role of Endoplasmic Reticulum Calcium Channels in Cone Degeneration Resulting from CNG Channel Deficiency
Role: Principal Investigator
Funding: UNIV OF OKLAHOMA NORMAN via NATL INST OF HLTH NEI
Oct 2016 – Jan 2018
Testing Sanofi-Genzyme Gene Therapy Vectors
Role: Principal Investigator
Funding: GENZYME CORP
Aug 2016 – May 2020
Development of Allele Independent Gene Therapy Strategies for Autosomal Dominant Retinitis Pigmentsa
Role: Other
Funding: NATL INST OF HLTH NEI
Aug 2016 – Jul 2022
Testing Gene Therapy in Models of Geographic Atrophy
Role: Principal Investigator
Funding: NATL INST OF HLTH NEI
Aug 2016 – May 2019
mTORC1-TFEB pathway in degeneration of the RPE
Role: Principal Investigator
Funding: UNIVERSITY OF TEXAS MEDICAL BRANCH via NATL INST OF HLTH NEI
Aug 2016 – Aug 2018
Defining oxidative stress induced changes in RPE that control RPE and photoreceptor degeneration
Role: Other
Funding: NATL INST OF HLTH NEI
Jun 2016 – Oct 2016
Testing hypoxia regulated endostatin vector in a mouse model of laser induced choroidal neovascularization
Role: Principal Investigator
Funding: FL ATLANTIC UNIV
Jan 2016 – Feb 2018
AAV-Mediated Therapy for Best Vitelliform Macular Dystrophy
Role: Co-Investigator
Funding: UNIV OF PENNSYLVANIA via FOU FOR FIGHTING BLINDNESS
Sep 2015 – Aug 2016
Translational Research for Retinal Degenerative Therapies
Role: Project Manager
Funding: UNIV OF PENNSYLVANIA via NATL INST OF HLTH NEI
Jul 2015 – Dec 2017
A Novel Antioxidant Therapy for Retinal Degeneration
Role: Principal Investigator
Funding: BRIGHTFOCUS FOU
Jun 2015 – Jun 2018
Testing of Shire 005825 in P23H Transgenic Mice
Role: Principal Investigator
Funding: SHIRE HUMAN GENETIC THERAPIES INC
Apr 2015 – Oct 2016
Testing zeaxanthin in a mouse model of geographic atrophy
Role: Principal Investigator
Funding: ZEAVISION LLC
Sep 2014 – Aug 2016
Regulation of Stromal Wound Healing by Growth Factors
Role: Project Manager
Funding: NATL INST OF HLTH NEI
Sep 2014 – Feb 2017
Translating Gene Therapy for RHO adRP to the Clinic
Role: Principal Investigator
Funding: FOU FOR FIGHTING BLINDNESS
Jul 2013 – Jun 2020
Age Related Macular Degeneration Research and Education
Role: Principal Investigator
Funding: UF FOUNDATION
Mar 2012 – Feb 2018
Translational Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa
Role: Principal Investigator
Funding: UNIV OF PENNSYLVANIA via NATL INST OF HLTH
Mar 2011 – Feb 2016
Mitochondrial Oxidative Stress in the Retinal Pigment Epithelium as a Model for Atrophic Macular Degeneration
Role: Principal Investigator
Funding: NATL INST OF HLTH NEI
Jan 2008 – May 2022
Shaler Richards Professorship #1
Role: Principal Investigator
Funding: UF FOUNDATION

Contact Details

Emails:
Business:
lewin@mgm.ufl.edu
Addresses:
Business Mailing:
PO Box 100266
GAINESVILLE FL 32610
Business Street:
R1-295 ARB
GAINESVILLE FL 326100266