Jean Bennett

Jean Bennett is the F. M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania. Her research focuses on gene therapy for retinal diseases. Her laboratory developed the first FDA approved gene therapy for use in humans, which treats a rare form of blindness.

Not to be confused with Jean M. Bennett.

Education

Bennett graduated with honors with her bachelor of science in biology from Yale University in 1976. In 1980, she obtained a Doctorate of Philosophy in Zoology; Cell And Development Biology from the University of California, Berkeley. Bennett continued on to Harvard University to receive her Doctor of Medicine (M.D.) in 1986.

Career

Early research

Bennett received her PhD in Zoology from the University of California, Berkeley in 1980. under Dr. Daniel Mazia. Her graduate research focused on the early development of sea urchin embryos. She moved on to postdoctoral work at the University of California, San Francisco under the guide of Dr. Roger Pedersen. As a postdoc, she collaborated with Dr. William French Anderson developing molecular techniques for gene editing. In 1982, she left this position to attend medical school at Harvard University.[1]

At Harvard, Bennett studied human genetics with. Leon Rosenberg and Wayne Fenton (Yale), and she also investigated Down's syndrome and Alzheimer's disease with John Gearhart, Mary Lou Oster-Granite, and Roger Reeves (Johns Hopkins). From this work, she was awarded a career development grant from the Foundation Fighting Blindness to begin research on gene therapy for retinitis pigmentosa (genetic blindness).

Development of Luxturna

To develop an effective gene therapy in the retina, Bennett started by investigating adenoviruses and adeno-associated viruses (AAV) for gene editing in mice and non-human primates at the Institute for Human Gene Therapy at the University of Pennsylvania.[2][3][4][5][6] The field of gene therapy was stymied after the death of Jesse Gelsinger during 1999 in a clinical trial for gene editing.[7] However, Bennett pushed forward and demonstrated that AAV-mediated delivery of a functional RPE65 gene significantly improved sight in near-blind dogs.[8]

Based on their pre-clinical data, Bennett's team pursued clinical trials in children with a defective form of the RPE65 gene. Their initial trials showed a stark improvement in light sensitivity and visual function in these children.[9][10][11][12][13] Based on this, the therapy, marketed as LUXTURNA®, was approved by the FDA for use in humans. Currently, her laboratory is investigating gene therapy approaches for other retinal diseases.[14][15][16]

    Awards and patents

    Awards

    Patents
    • Method of treating or retarding the development of blindness, (Application US12/832,282) [20]
    • Methods, systems, and computer readable media for testing visual function using virtual mobility tests (Application PCT/US2019/029173 )[21]
    • Trans-viral vector mediated gene transfer to the retina, (Application US10/140,227) [22]
    • Modified aav8 capsid for gene transfer for retinal therapies (Application EP14749120.3A) [23]
    • Proviral plasmids and production of recombinant adeno-associated virus (Application US14/117,312 events) [24]
    • Method of treating or retarding the development of blindness (Application AU2002256162A)[25]
    • Gene therapy for ocular disorders (Application PCT/US2018/037592) [26]
    • Gene therapy for treating peroxisomal disorders (Application PCT/CA2018/050642)[27]
    • Trans-splicing molecules (Application PCT/US2019/027981)[28]
    • Gene therapy for ocular disorders (Application PCT/US2018/029167)[29]
    • Syringe actuator (Application PCT/US2010/022209)[30]
    • Methods and Compositions for Treatment of Disorders and Diseases Involving RDH12 (Application US16/314,179)[31]
    • Gene therapy for ocular disorders, pending (Application US16/489,770) [32]
    • Enhanced AAV-mediated gene transfer for retinal therapies (Application US15/246,001)[33]
    • Synergistic combination of neuronal viability factors and uses thereof (Application US15/576,027)[34]
    • Aav vectors expressing sec10 for treating kidney damage (Application US14/789,159)[35]
    • Methods and compositions for treatment of ocular disorders and blinding diseases (Application US16/066,970)[36]
    • Apparatus and methods for testing visual function and functional vision at varying luminance levels (Application US15/662,153)[37]
    • Compositions and Methods for Correction of Heritable Ocular Disease (Application US15/776,663)[38]
    • Vision test for determining retinal disease progression (Application PCT/US2015/058958) [39]
    • Compositions and methods for self-regulated inducible gene expression (Application US15/500,591)[40]
    • Aav7 viral vectors for targeted delivery of rpe cells (Application PCT/US2009/041606)[41]
    • Method for transducing cells with primary cilia (Application US12/601,898)[42]
    • Compositions and methods for treatment of disorders related to CEP290 (Application US14/904,447)[43]
    • Rapidly deployable modular shelter system (Application US16/287,539)[44]

    References
    1. Bennett, Jean (2014-08-01). "My Career Path for Developing Gene Therapy for Blinding Diseases: The Importance of Mentors, Collaborators, and Opportunities". Human Gene Therapy. 25 (8): 663–670. doi:10.1089/hum.2014.2529. ISSN 1043-0342. PMC 4137328. PMID 25136912.
    2. Bennett, J.; Tanabe, T.; Sun, D.; Zeng, Y.; Kjeldbye, H.; Gouras, P.; Maguire, A. M. (June 1996). "Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy". Nature Medicine. 2 (6): 649–654. doi:10.1038/nm0696-649. ISSN 1078-8956. PMID 8640555.
    3. Bennett, J.; Duan, D.; Engelhardt, J. F.; Maguire, A. M. (December 1997). "Real-time, noninvasive in vivo assessment of adeno-associated virus-mediated retinal transduction". Investigative Ophthalmology & Visual Science. 38 (13): 2857–2863. ISSN 0146-0404. PMID 9418740.
    4. Bennett, J.; Maguire, A. M.; Cideciyan, A. V.; Schnell, M.; Glover, E.; Anand, V.; Aleman, T. S.; Chirmule, N.; Gupta, A. R.; Huang, Y.; Gao, G. P. (1999-08-17). "Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9920–9925. doi:10.1073/pnas.96.17.9920. ISSN 0027-8424. PMC 22311. PMID 10449795.
    5. Bennett, J.; Anand, V.; Acland, G. M.; Maguire, A. M. (2000). "Cross-species comparison of in vivo reporter gene expression after recombinant adeno-associated virus-mediated retinal transduction". Methods in Enzymology. 316: 777–789. doi:10.1016/s0076-6879(00)16762-x. ISSN 0076-6879. PMID 10800714.
    6. Bennett, J.; Maguire, A. M.; Cideciyan, A. V.; Schnell, M.; Glover, E.; Anand, V.; Aleman, T. S.; Chirmule, N.; Gupta, A. R.; Huang, Y.; Gao, G. P. (1999-08-17). "Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina". Proceedings of the National Academy of Sciences of the United States of America. 96 (17): 9920–9925. doi:10.1073/pnas.96.17.9920. ISSN 0027-8424. PMC 22311. PMID 10449795.
    7. Wade, Nicholas (1999-09-29). "Patient Dies During a Trial Of Therapy Using Genes". The New York Times. ISSN 0362-4331. Retrieved 2020-02-01.
    8. Acland, G. M.; Aguirre, G. D.; Ray, J.; Zhang, Q.; Aleman, T. S.; Cideciyan, A. V.; Pearce-Kelling, S. E.; Anand, V.; Zeng, Y.; Maguire, A. M.; Jacobson, S. G. (May 2001). "Gene therapy restores vision in a canine model of childhood blindness". Nature Genetics. 28 (1): 92–95. doi:10.1038/ng0501-92. ISSN 1061-4036. PMID 11326284.
    9. Maguire, Albert M.; Simonelli, Francesca; Pierce, Eric A.; Pugh, Edward N.; Mingozzi, Federico; Bennicelli, Jeannette; Banfi, Sandro; Marshall, Kathleen A.; Testa, Francesco; Surace, Enrico M.; Rossi, Settimio (2008-05-22). "Safety and efficacy of gene transfer for Leber's congenital amaurosis". The New England Journal of Medicine. 358 (21): 2240–2248. doi:10.1056/NEJMoa0802315. ISSN 1533-4406. PMC 2829748. PMID 18441370.
    10. Maguire, Albert M.; High, Katherine A.; Auricchio, Alberto; Wright, J. Fraser; Pierce, Eric A.; Testa, Francesco; Mingozzi, Federico; Bennicelli, Jeannette L.; Ying, Gui-shuang; Rossi, Settimio; Fulton, Ann (2009-11-07). "Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial". Lancet. 374 (9701): 1597–1605. doi:10.1016/S0140-6736(09)61836-5. ISSN 1474-547X. PMC 4492302. PMID 19854499.
    11. Cideciyan, Artur V.; Aleman, Tomas S.; Boye, Sanford L.; Schwartz, Sharon B.; Kaushal, Shalesh; Roman, Alejandro J.; Pang, Ji-Jing; Sumaroka, Alexander; Windsor, Elizabeth A. M.; Wilson, James M.; Flotte, Terence R. (2008-09-30). "Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics". Proceedings of the National Academy of Sciences of the United States of America. 105 (39): 15112–15117. doi:10.1073/pnas.0807027105. ISSN 1091-6490. PMC 2567501. PMID 18809924.
    12. Maguire, Albert M.; Simonelli, Francesca; Pierce, Eric A.; Pugh, Edward N.; Mingozzi, Federico; Bennicelli, Jeannette; Banfi, Sandro; Marshall, Kathleen A.; Testa, Francesco; Surace, Enrico M.; Rossi, Settimio (2008-05-22). "Safety and efficacy of gene transfer for Leber's congenital amaurosis". The New England Journal of Medicine. 358 (21): 2240–2248. doi:10.1056/NEJMoa0802315. ISSN 1533-4406. PMC 2829748. PMID 18441370.
    13. Bainbridge, James W. B.; Smith, Alexander J.; Barker, Susie S.; Robbie, Scott; Henderson, Robert; Balaggan, Kamaljit; Viswanathan, Ananth; Holder, Graham E.; Stockman, Andrew; Tyler, Nick; Petersen-Jones, Simon (2008-05-22). "Effect of gene therapy on visual function in Leber's congenital amaurosis". The New England Journal of Medicine. 358 (21): 2231–2239. doi:10.1056/NEJMoa0802268. ISSN 1533-4406. PMID 18441371.
    14. Isgrig, Kevin; McDougald, Devin S.; Zhu, Jianliang; Wang, Hong Jun; Bennett, Jean; Chien, Wade W. (2019-01-25). "AAV2.7m8 is a powerful viral vector for inner ear gene therapy". Nature Communications. 10 (1): 427. doi:10.1038/s41467-018-08243-1. ISSN 2041-1723. PMC 6347594. PMID 30683875.
    15. McDougald, Devin S.; Duong, Thu T.; Palozola, Katherine C.; Marsh, Anson; Papp, Tyler E.; Mills, Jason A.; Zhou, Shangzhen; Bennett, Jean (2019-06-14). "CRISPR Activation Enhances In Vitro Potency of AAV Vectors Driven by Tissue-Specific Promoters". Molecular Therapy - Methods & Clinical Development. 13: 380–389. doi:10.1016/j.omtm.2019.03.004. ISSN 2329-0501. PMID 31024980.
    16. Duong, Thu T.; Lim, James; Vasireddy, Vidyullatha; Papp, Tyler; Nguyen, Hung; Leo, Lanfranco; Pan, Jieyan; Zhou, Shangzhen; Chen, H. Isaac (2019). "Comparative AAV-eGFP Transgene Expression Using Vector Serotypes 1–9, 7m8, and 8b in Human Pluripotent Stem Cells, RPEs, and Human and Rat Cortical Neurons". Stem Cells International. Retrieved 2020-02-01.
    17. "Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award". Smithsonian Magazine. Retrieved 2020-01-31.
    18. "Three Penn Medicine Gene Therapy Innovators Receive International Award for Pioneering Work to Treat Childhood Blindness – PR News". www.pennmedicine.org. Retrieved 2020-02-01.
    19. "Pioneer in Ocular Gene Therapy to Receive 2018 Marion Spencer Fay Award". DrexelNow. 2018-09-14. Retrieved 2020-02-01.
    20. , "Method of treating or retarding the development of blindness", issued 2010-07-08
    21. , "Methods, systems, and computer readable media for testing visual function using virtual mobility tests", issued 2019-04-25
    22. , "Trans-viral vector mediated gene transfer to the retina", issued 2002-05-07
    23. , "Modified aav8 capsid for gene transfer for retinal therapies", issued 2014-02-07
    24. , "Proviral plasmids and production of recombinant adeno-associated virus", issued 2012-05-16
    25. , "Method of treating or retarding the development of blindness", issued 2002-04-11
    26. , "Gene therapy for ocular disorders", issued 2018-06-14
    27. , "Gene therapy for treating peroxisomal disorders", issued 2018-05-31
    28. , "Trans-splicing molecules", issued 2019-04-17
    29. , "Gene therapy for ocular disorders", issued 2018-04-24
    30. , "Syringe actuator", issued 2010-01-27
    31. , "Methods and Compositions for Treatment of Disorders and Diseases Involving RDH12", issued 2017-07-07
    32. , "Gene therapy for ocular disorders", issued 2018-03-01
    33. , "Enhanced AAV-mediated gene transfer for retinal therapies", issued 2016-08-24
    34. , "Synergistic combination of neuronal viability factors and uses thereof", issued 2016-05-20
    35. , "Aav vectors expressing sec10 for treating kidney damage", issued 2015-07-01
    36. , "Methods and compositions for treatment of ocular disorders and blinding diseases", issued 2017-01-05
    37. , "Apparatus and methods for testing visual function and functional vision at varying luminance levels", issued 2017-07-27
    38. , "Compositions and Methods for Correction of Heritable Ocular Disease", issued 2016-11-18
    39. , "Vision test for determining retinal disease progression", issued 2015-11-04
    40. , "Compositions and methods for self-regulated inducible gene expression", issued 2015-07-31
    41. , "Aav7 viral vectors for targeted delivery of rpe cells", issued 2009-04-24
    42. , "method for transducing cells with primary cilia", issued 2008-05-30
    43. , "Compositions and methods for treatment of disorders related to CEP290", issued 2014-07-11
    44. , "Rapidly deployable modular shelter system", issued 2019-02-27
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