- 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.
Rotation Projects for 2010-2011
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
Jacobs JB, Dell'Osso LF, Wang ZI, Acland GM, Bennett J. : Using the NAFX tomeasure the effectiveness over time of gene therapy in canine LCA. Invest Ophthalmol Vis Sci 50.(10): 4685-92, Oct 2009.
Zhang, Y, Singh, MK, Bennett, J, Yoshida,Y, Epstein, JA: Tie2 Cre-mediated inactivation of PlexinD1 results in congenital heart, vascular and skeletal defects. Dev Bio 325(1): 82-103, 2009.
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. : Safety and efficacy of gene transfer for Leber's
N Engl J Med. 358: .(21): 240-8, May 2008.
Edo M, Zoltick PW, Chung DC, Bennett J, Flake AW: Gene transfer to ocular stem cells by early gestational intra-amniotic injection of lentiviral vector. Mol Ther 15(3): 579-587, March 2007.
Bennett J: Design of a gene therapy for Leber Congenital Amaurosis. Phacilitate. Baltimore, MD, January 2007.
Chung D, Askew C, Bedorsian J, Wei Z, Gratton MA, Lipschutz JH, Bennett J: Novel adeno-associated virus (AAV)-mediated transduction of cells with primary cilia: Applications for retinal, cochlear and renal disease. pre-ARVO 2007 Notes: submitted.
Bennett J, Bennicelli J, Wright F, Arruda VR, F.M. Kirby Study Group, Narfstrom K, Pugh EN, Jacobs J, Dell'Osso LF, Komaromy G, Acland G, High KH, and Maguire AM: Adeno-associated virus (AAV) for treatment of Leber Congenital Amaurosis (LCA-RPE65). ARVO 2007 Notes: submitted.
Rex TS, Lee V, Vandenberghe L, Chung D, Wei Z, Wilson JM, and Bennet J: Evaluation of hybrid adeno-associated virus (AAV)-mediated transduction of the fetal retina: Impact of single amino acid changes of the capsid. ASGT 2007 Notes: submitted.
Zelenaia O, Lui X, McDonnell J, Bennicelli J, Maguire AM, Bennett J, High KA, and Wright JF: Evaluation of devices for clinical administration of AAV2-hRPE65, an investigational gene therapy vector to treat Lebers Congenital Amaurosis. ASGT 2007 Notes: submitted.
Lee V, Vandenberghe LH, Chung D, Rex T, Wei Z, Wilson JM, and Bennett J: Novel Adeno-associated virus (AAV)-mediated transduction of the fetal retina: Impact of single amino acid changes of the capsid. pre-ARVO 2007 Notes: submitted.
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Last updated: 01/24/2014
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