- 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
Minella A L, Mowat F M, Willett K L, Sledge D, Bartoe J T, Bennett J, Petersen-Jones S M: Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials. Gene therapy 21(10): 913-20, Oct 2014.
Bennett Johan, De Cock Dries, Hiltrop Nick, Adriaenssens Tom: Unusual stent fracture: diagnosis with optical coherence tomography. Journal of cardiovascular medicine (Hagerstown, Md.) Sep 2014.
Cronin Therese, Vandenberghe Luk H, Hantz Péter, Juttner Josephine, Reimann Andreas, Kacsó Agota-Enikő, Huckfeldt Rachel M, Busskamp Volker, Kohler Hubertus, Lagali Pamela S, Roska Botond, Bennett Jean: Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter. EMBO molecular medicine 6(9): 1175-90, Sep 2014.
Adriaenssens Tom, Dens Jo, Ughi Giovanni, Bennett Johan, Dubois Christophe, Sinnaeve Peter, Wiyono Stefanus, Coosemans Mark, Belmans Ann, D'hooge Jan, Vrolix Mathias, Desmet Walter: Optical coherence tomography study of healing characteristics of paclitaxel-eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery rEstenosis) randomised clinical trial. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 10(4): 439-48, Aug 2014.
Bennett Jean: My career path for developing gene therapy for blinding diseases: the importance of mentors, collaborators, and opportunities. Human gene therapy 25(8): 663-70, Aug 2014.
Black Aaron, Vasireddy Vidyullatha, Chung Daniel C, Maguire Albert M, Gaddameedi Rajashekhar, Tolmachova Tania, Seabra Miguel, Bennett Jean: Adeno-associated virus 8-mediated gene therapy for choroideremia: preclinical studies in in vitro and in vivo models. The journal of gene medicine 16(5-6): 122-30, May-Jun 2014.
Huckfeldt Rachel M, Bennett Jean: Promising first steps in gene therapy for choroideremia. Human gene therapy 25(2): 96-7, Feb 2014.
Morgan Jessica I W, Han Grace, Klinman Eva, Maguire William M, Chung Daniel C, Maguire Albert M, Bennett Jean: High-resolution adaptive optics retinal imaging of cellular structure in choroideremia. Investigative ophthalmology & visual science 55(10): 6381-97, 2014.
Ashtari Manzar, Cyckowski Laura, Yazdi Alborz, Viands Amanda, Marshall Kathleen, Bókkon István, Maguire Albert, Bennett Jean: fMRI of retina-originated phosphenes experienced by patients with Leber congenital amaurosis. PloS one 9(1): e86068, 2014.
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.
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Last updated: 10/30/2014
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