Research Terms
Industries
Biswal MR, Ahmed CM, Ildefonso CJ, Han P, Li H, Jivanji H, Mao H, Lewin AS. Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress. Exp Eye Res. 2015 Nov;140:94-105. doi: 10.1016/j.exer.2015.07.022. Epub 2015 Aug 25. PubMed PMID: 26315784; PubMed Central PMCID: PMC4624518.
Ildefonso CJ, Jaime H, Biswal MR, Boye SE, Li Q, Hauswirth WW, Lewin AS. Gene therapy with the caspase activation and recruitment domain reduces the ocular inflammatory response. Mol Ther. 2015 May;23(5):875-84. doi: 10.1038/mt.2015.30. Epub 2015 Feb 20. PubMed PMID: 25698151; PubMed Central PMCID: PMC4427880.
Ildefonso CJ, Jaime H, Rahman MM, Li Q, Boye SE, Hauswirth WW, Lucas AR, McFadden G, Lewin AS. Gene delivery of a viral anti-inflammatory protein to combat ocular inflammation. Hum Gene Ther. 2015 Jan;26(1):59-68. doi: 10.1089/hum.2014.089. PubMed PMID: 25420215; PubMed Central PMCID: PMC4303190.
Rossmiller BP, Ryals RC, Lewin AS. Gene therapy to rescue retinal degeneration caused by mutations in rhodopsin. Methods Mol Biol. 2015;1271:391-410. doi: 10.1007/978-1-4939-2330-4_25. PubMed PMID: 25697537; PubMed Central PMCID: PMC4696870.
Koilkonda R, Yu H, Talla V, Porciatti V, Feuer WJ, Hauswirth WW, Chiodo V, Erger KE, Boye SL, Lewin AS, Conlon TJ, Renner L, Neuringer M, Detrisac C, Guy J. LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile. Invest Ophthalmol Vis Sci. 2014 Oct 23;55(12):7739-53. doi: 10.1167/iovs.14-15388. PubMed PMID: 25342621; PubMed Central PMCID: PMC4249950.
Sriram S, Gibson DJ, Robinson P, Pi L, Tuli S, Lewin AS, Schultz G. Assessment of anti-scarring therapies in ex vivo organ cultured rabbit corneas. Exp Eye Res. 2014 Aug;125:173-82. doi: 10.1016/j.exer.2014.06.014. Epub 2014 Jun 24. PubMed PMID: 24971495; PubMed Central PMCID: PMC4496961.
Lewin AS, Rossmiller B, Mao H. Gene augmentation for adRP mutations in RHO. Cold Spring Harb Perspect Med. 2014 Jul 18;4(9):a017400. doi: 10.1101/cshperspect.a017400. Review. PubMed PMID: 25037104; PubMed Central PMCID: PMC4143106.
Mao H, Seo SJ, Biswal MR, Li H, Conners M, Nandyala A, Jones K, Le YZ, Lewin AS. Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration. Invest Ophthalmol Vis Sci. 2014 Jul 1;55(7):4613-27. doi: 10.1167/iovs.14-14633. PubMed PMID: 24985474; PubMed Central PMCID: PMC4112607.
Rowe-Rendleman CL, Durazo SA, Kompella UB, Rittenhouse KD, Di Polo A, Weiner AL, Grossniklaus HE, Naash MI, Lewin AS, Horsager A, Edelhauser HF. Drug and gene delivery to the back of the eye: from bench to bedside. Invest Ophthalmol Vis Sci. 2014 Apr 28;55(4):2714-30. doi: 10.1167/iovs.13-13707. Review. PubMed PMID: 24777644; PubMed Central PMCID: PMC4004426.
Koilkonda RD, Yu H, Chou TH, Feuer WJ, Ruggeri M, Porciatti V, Tse D, Hauswirth WW, Chiodo V, Boye SL, Lewin AS, Neuringer M, Renner L, Guy J. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial. JAMA Ophthalmol. 2014 Apr 1;132(4):409-20. doi: 10.1001/jamaophthalmol.2013.7630. PubMed PMID: 24457989; PubMed Central PMCID: PMC4266107.
Choudhury S, Nashine S, Bhootada Y, Kunte MM, Gorbatyuk O, Lewin AS, Gorbatyuk M. Modulation of the rate of retinal degeneration in T17M RHO mice by reprogramming the unfolded protein response. Adv Exp Med Biol. 2014;801:455-62. doi: 10.1007/978-1-4614-3209-8_58. PubMed PMID: 24664731; PubMed Central PMCID: PMC4083741.
Mitter SK, Song C, Qi X, Mao H, Rao H, Akin D, Lewin A, Grant M, Dunn W Jr, Ding J, Bowes Rickman C, Boulton M. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD. Autophagy. 2014;10(11):1989-2005. doi: 10.4161/auto.36184. PubMed PMID: 25484094; PubMed Central PMCID: PMC4502658.
Sriram S, Robinson P, Pi L, Lewin AS, Schultz G. 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. 2013; 54(13):8214-23. PubMed [journal] PMID: 24282226, PMCID: PMC3867185
American Society for Gene and Cell Therapy, Member; 2003 - 2017
Association for Research in Vision and Ophthalmology, Member; 1995 - 2017
American Association for the Advancement of Science, Member; 1983 - 2017
American Society for Microbiology, Member; 1983 - 2017
American Society of Biochemists and Molecular Biologists, Member; 1983 - 2017
Diseases and Pathophysiology of the Visual System (DPVS) Study Section, National Institutes of Health; 2012 - 2016
Macular Degeneration Grant Program, BrightFocus Foundation; 2010 - 2017
Small Business Innovation Research Program /Small Business Technology Transfer Program , National Institutes of Health; 2000 - 2011
Pharmacological Approaches to Treatment in a Mouse Model of Dry AMD; Seminar; Alcon Laboratories; 2012
Testing Therapy in Mouse Model of Atrophic Macular Degeneration; Seminar; Georgia Health Sciences University; 2012
Testing Gene Therapy in Animal Models of Autosomal Dominant and X-linked Retinitis Pigmentosa; International Congress on Research of Rare and Orphan Diseases; Blackswan Foundation; 2012
Gene Therapy in Animal Models of Autosomal Dominant and X-linked Retinitis Pigmentosa; Seminar; Telethon Institute of Genetics & Medicine, Naples, Italy; 2012
Viral vector design and clinical translation for gene therapy; Conference on Drug and Gene Delivery to the Back of the Eye; Association for Research in Vision and Ophthalmology; 2012
Description of our current research on gene therapy for this inherited retinal degenerative disease.
Subject Areas:
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Audience:
Adults
Duration:
1 hour or less
Fee:
Expenses Only
Description of our research to develop treatments for dry age related macular degeneration.
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Audience:
Adults
Duration:
1 hour or less
Fee:
Expenses Only
Discussion of the cause of age related macular degeneration, what treatments are available and what new treatments may become available based on current research.
Subject Areas:
Keywords:
Audience:
Adults
Duration:
1 hour or less
Fee:
No Cost
This AAV gene therapy approach provides a one-time treatment to oxidative stress. Sustained oxidative stress can lead to a variety of pathophysiological diseases including age-related macular degeneration, diabetic retinopathy, and amyotrophic lateral sclerosis. In the United States, age-related macular degeneration affects 1.75 million people and diabetic retinopathy affects 10 million. When the human body overproduces reactive oxygen species and reactive nitrogen species, it can lead to the oxidation and degradation of proteins, lipids, and DNA in the body. This degradation of DNA and lipids can cause mutations in the DNA sequences, and damaged cellular components can induce an inflammatory reaction. Researchers at the University of Florida have developed an AAV vector that introduces a small protein into the patient’s cells that promotes the production of detoxifying enzymes in the body. The AAV vector only requires one injection to deliver the secreted and cell-penetrating protein into the patient’s tissue. Unlike current methods that require monthly intraocular injections, this treatment for age-related macular degeneration is a one-time treatment for oxidative stress.
Effective treatment for pathophysiologic diseases attributed to sustained oxidative stress, including age-related macular degeneration, diabetic retinopathy, and neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson's Disease and Alzheimer's Disease
This AAV vector delivers a secreted and cell-penetrating peptide to inhibit reaction to oxidative stress. Nrf2-Keap1 is a signaling pathway that regulates the expression of detoxifying enzymes, or antioxidants. Keap1, by reducing the levels of the Nrf2, maintains a constant level of this antioxidant production. Researchers at the University of Florida have developed an AAV vector that acts as a delivery system to introduce a peptide that allows Nrf2 to increase detoxifying enzyme production. The peptide binds with the Keap1. As a result, free Nrf2 transcription factor is able to translocate to the nucleus of the cell and stimulate expression of detoxifying enzymes. AAV are small DNA viruses that do not integrate into the genome of the cells they infect. They are used in gene therapy treatments because of their ability to infect a wide spectrum of cells with minimal inflammatory response. This virus does not cause disease.
This small peptide expression technique effectively expresses small peptides through gene delivery in mammalian cells providing promising targets for therapeutic interventions for many pathological conditions. The use of peptides as mainstream drug candidates has been hampered by their low bioavailability, short half-life, and potential immune responses following repeated administration. Researchers at the University of Florida have designed an expression technique that allows for continuous and high-level expression of short peptides. This device can be used as a research tool for developing pharmacological agents targeting many pathological processes including hypertension, cancer, tumor-specific angiogenesis, neurodegenerative disorders, diabetes and diabetic complications. The technique also has therapeutic potential in its own right as a platform for peptide delivery.
Research of numerous biological processes in mammalian cells and treatment of various diseases using peptide-based therapies
The drug delivery market is constantly growing and changing as new developments arise. It is important to employ the most effective and efficient treatment available to patients. Currently, when the superior form or treatment is small peptides, they are unavailable to patients because they are difficult to produce in large amounts and difficult to deliver to target cells. With this technology, it is possible to continuously produce small peptides in large quantities in situ in a cost effective manner. Using this system, a plasmid will be available for use in both in vitro and in vivo studies.