- Molecular genetics of retinal degenerations.
- Gene therapy-mediated treatment of ocular disease.
Retina, Neovascularization, Neuronal Degeneration, Gene Therapy, Viral Vector, AAV, Lentivirus, Adenovirus, Vision, Animal Models, Eye, Immune Response.
Description of Research
Jean Bennett studies the molecular genetics of inherited retinal degenerations with the idea of using this knowledge to develop rational approaches for treatment of these diseases. Target diseases include retinitis pigmentosa and age-related macular degeneration. Studies in her laboratory range from identifying the molecular bases of retinal degenerations, generating animal models for these diseases, evaluating novel vectors for retinal gene transfer, characterizing immune responses to gene transfer, developing novel gene-based approaches for reversal of sensory loss, and rescuing vision in animal models through gene based treatments. Dr. Bennett was one of the first investigators to use viral vectors to deliver transgenes to specific cells in the retina and also led the first team to demonstrate proof-of-principle of ocular gene therapy. She has developed a number of strategies for gene therapy-mediated treatments for retinal disease. Besides the eye, projects in Dr. Bennett's laboratory target other diseases/organs suffering from mutations in cilia proteins, including the ear (cochlea) and the kidney (renal tubular epithelium). Dr. Bennett's work leads naturally to translational research. For example, a study conducted in her lab and with collaborators at UPenn, Cornell and University of Florida led to a remarkable reversal of blindness in a canine model of a blinding disease affecting infants. This treatment is currently being tested in human clinical trials at several different Centers. Dr. Bennett is Scientific Director for the Phase I/II human clinical trial evaluating the safety and efficacy of gene transfer in Leber congenital amaurosis (LCA) due to RPE65 mutations. This trial is being carried out at The Children's Hospital of PHiladelphia (CHOP). This was the first study to report the exciting efficacy results in all twelve subjects, including 5 children.
Gene therapy for an inherited retinal degeneration; Gene therapy for retinal neovascularization; Generation of a mouse model for an inherited macular degeneration; Gene therapy for Leber Congenital Amaurosis, Gene Therapy for autosomal recessive Stargartd Disease; Gene Therapy for Choroideremia; Immune response to subretinal readministration of gene therapy vectors; Identification of novel genes causing retinal degeneration; Gene Therapy for Usher's Syndrome (blindness and deafness)
Ik Joon Chang
Rob Collin (visiting from Rabhoud University, The Netherlands)
William M. Maguire
Translational research on retinal degenerations
Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, Elci OU, Chung DC, Sun J, Wright JF, Cross DR, Aravand P, Cyckowski LL, Bennicelli JL, Mingozzi F, Auricchio A, Pierce EA, Ruggiero J, Leroy BP, Simonelli F, High KA, Maguire AM: Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet 388(10045): 661072, Aug 2016.
Duong Thu T, Vasireddy Vidyullatha, Mills Jason A, Bennett Jean: Retinas in a Dish Peek into Inherited Retinal Degeneration. Cell stem cell 18(6): 688-9, Jun 2016.
Mei X, Chaffiol A, Kole C, Yang Y, Millet-Puel G, Clérin E, Aït-Ali N, Bennett J, Dalkara D, Sahel JA, Duebel J, Léveillard T: The Thioredoxin Encoded by the Rod-Derived Cone Viability Factor Gene Protects Cone Photoreceptors Against Oxidative Stress. Antioxid Redox Signal 24(16): 909-23, June 2016.
Palfi A, Chadderton N, O'Reilly M, Nagel-Wolfrum K, Wolfrum U, Bennett J, Humphries P, Kenna P, Millington-Ward S, Farrar J: Corrigendum to "Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho-/- mouse". Molecular therapy. Methods & clinical development 3: 16032, May 2016.
Garanto Alejandro, Chung Daniel C, Duijkers Lonneke, Corral-Serrano Julio C, Messchaert Muriël, Xiao Ru, Bennett Jean, Vandenberghe Luk H, Collin Rob W: In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery. Human molecular genetics Apr 2016 Notes: Epub ahead of print.
Shah Neepa, Damani Mausam R, Zhu Xiaosong Sonia, Bedoukian Emma C, Bennett Jean, Maguire Albert M, Leroy Bart P: Isolated maculopathy associated with biallelic CRB1 mutations. Ophthalmic genetics Page: 1-4, Apr 2016 Notes: Epub ahead of print.
Maguire, AM, Russell, SR, Haller, JA, Sohn, ES, Mahajan, VB, Bennett, J: Subretinal injection technique for tretinal gene therapy application. Macula Society, Florida 2016 Notes: Poster.
Testa Francesco, Maguire Albert M, Rossi Settimio, Marshall Kathleen, Auricchio Alberto, Melillo Paolo, Bennett Jean, Simonelli Francesca: Evaluation of Ocular Gene Therapy in an Italian Patient Affected by Congenital Leber Amaurosis Type 2 Treated in Both Eyes. Advances in experimental medicine and biology 854: 533-9, 2016.
Ashtari, M, Cook, P, Zhang, H, Cyckowski, L, Nikonova, E, Young, G, Marshall, K, Gee, J, Leopold, D, Baker, C, Maguire, A, Bennett, J
: Plasticitiy of the human visual pathways in low vision subjects before and after retinal gene therapy.
Organization for Human Brain Mapping, Geneva, Switzerland 2016 Notes: Poster.
Russell, SR, Bennett, J, High, KA, Chung, DC, Wellman, JA, Maguire, AM : Phase 3 trial of AAV2-hRPE65v2 (SPK-RPE65) to treat RPE65 mutation-associated inherited retinal dystrophies. Saudi Ophthalmologic Society 2016 Notes: Poster.
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Last updated: 11/03/2016
The Trustees of the University of Pennsylvania