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. She was elected a member of the National Academy of Sciences in 2022.[1]

Education

Bennett graduated with honors from Yale University in 1976, with a bachelor of science in biology. Her father, William R. Bennett Jr., was a member of the faculty there. 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 (MD) 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 postdoctoral student, 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.[2]

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.[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] 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.[13][14][15]

Awards and patents

Awards

Patents

  • Method of treating or retarding the development of blindness, (2012).[19]
  • Methods, systems, and computer readable media for testing visual function using virtual mobility tests, (2019).[20]
  • Trans-viral vector mediated gene transfer to the retina, (abandoned).[21]
  • Modified AAV8 capsid for gene transfer for retinal therapies, (2015).[22]
  • Proviral plasmids and production of recombinant adeno-associated virus, (2016).[23]
  • Method of treating or retarding the development of blindness, (abandoned).[24]
  • Gene therapy for ocular disorders, (2018).[25]
  • Gene therapy for treating peroxisomal disorders, (2018).[26]
  • Trans-splicing molecules, (2019).[27]
  • Gene therapy for ocular disorders, (2018).[28]
  • Syringe actuator, (2010).[29]
  • Methods and compositions for treatment of disorders and diseases involving RDH12, (2019).[30]
  • Gene therapy for ocular disorders, (2018).[31]
  • Enhanced AAV-mediated gene transfer for retinal therapies, (2019).[32]
  • Synergistic combination of neuronal viability factors and uses thereof, (2020).[33]
  • AAV vectors expressing Sec10 for treating kidney damage, (abandoned).[34]
  • Methods and compositions for treatment of ocular disorders and blinding diseases, (2020).[35]
  • Apparatus and methods for testing visual function and functional vision at varying luminance levels, (2019).[36]
  • Compositions and methods for correction of heritable ocular disease, (2021).[37]
  • Vision test for determining retinal disease progression, (2021).[38]
  • Compositions and methods for self-regulated inducible gene expression, (2019).[39]
  • AAV7 viral vectors for targeted delivery of RPE cells (Application PCT/US2009/041606)[40]
  • Method for transducing cells with primary cilia, (2020).[41]
  • Compositions and methods for treatment of disorders related to CEP290, (2018).[42]

References

  1. ↑ "2022 NAS Election".
  2. ↑ 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.
  3. ↑ 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. S2CID 9184060.
  4. ↑ 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.
  5. ↑ 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. Bibcode:1999PNAS...96.9920B. doi:10.1073/pnas.96.17.9920. ISSN 0027-8424. PMC 22311. PMID 10449795.
  6. ↑ 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. Vol. 316. pp. 777–789. doi:10.1016/s0076-6879(00)16762-x. ISSN 0076-6879. PMID 10800714.
  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. S2CID 13105734.
  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. Bibcode:2008PNAS..10515112C. doi:10.1073/pnas.0807027105. ISSN 1091-6490. PMC 2567501. PMID 18809924.
  12. ↑ 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. hdl:10261/271174. ISSN 1533-4406. PMID 18441371.
  13. ↑ 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. Bibcode:2019NatCo..10..427I. doi:10.1038/s41467-018-08243-1. ISSN 2041-1723. PMC 6347594. PMID 30683875.
  14. ↑ 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. PMC 6477656. PMID 31024980.
  15. ↑ 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. 2019: 1–11. doi:10.1155/2019/7281912. PMC 6360060. PMID 30800164.
  16. ↑ "Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award". Smithsonian Magazine. Retrieved 2020-01-31.
  17. ↑ "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.
  18. ↑ "Pioneer in Ocular Gene Therapy to Receive 2018 Marion Spencer Fay Award". DrexelNow. 2018-09-14. Retrieved 2020-02-01.
  19. ↑ US 8147823, Acland, Gregory M.; Aguirre, Gustavo D. & Bennett, Jean et al., "Method of treating or retarding the development of blindness", published 2012-04-03, assigned to The Trustees of the University of Pennsylvania, University of Florida Research Foundation Inc. and Cornell Research Foundation Inc.
  20. ↑ WO application 2019210087, Bennett, Jean; Aleman, Tomas S. & Ashtari, Manzar et al., "Methods, systems, and computer readable media for testing visual function using virtual mobility tests", published 2019-10-31, assigned to The Trustees of the University of Pennsylvania
  21. ↑ US 2003003582, Wakefield, John & Bennett, Jean, "Trans-viral vector mediated gene transfer to the retina", issued 2003-01-02, assigned to Tranzyme Inc.
  22. ↑ EP 2954051, Cronin, Therese; Bennett, Jean & Vandenberghe, Luk E., "Modified AAV8 capsid for gene transfer for retinal therapies", issued 2015-12-16, assigned to The Trustees of the University of Pennsylvania
  23. ↑ US 9249425, Bennett, Jean & Bennicelli, Jeannette L., "Proviral plasmids and production of recombinant adeno-associated virus", published 2016-02-02, assigned to The Trustees of the University of Pennsylvania & inventors
  24. ↑ WO 02082904, Acland, Gregory M.; Aguirre, Gustavo D. & Bennett, Jean et al., "Method of treating or retarding the development of blindness", published 2002-10-24, assigned to The Trustees of the University of Pennsylvania, University of Florida Research Foundation Inc. and Cornell Research Foundation Inc.
  25. ↑ WO application 2018232149, Bennett, Jean; Sun, Junwei & Bennicelli, Jeannette, "Gene therapy for ocular disorders", published 2018-12-20, assigned to The Trustees of the University of Pennsylvania
  26. ↑ WO application 2018218359, Bennett, Jean; Sun, Junwei & Song, Ji Yun et al., "Gene therapy for treating peroxisomal disorders", published 2018-12-06, assigned to The Trustees of the University of Pennsylvania, the inventors, Nancy Braverman,Catherine Argyriou and Joseph Hacia
  27. ↑ WO application 2019204514, Johnson, Philip R.; SCchnepp, Bruce C. & Bennett, Jean et al., "Trans-splicing molecules", published 2019-04-17, assigned to The Trustees of the University of Pennsylvania and Limelight Bio Inc.
  28. ↑ WO application 2018200542, Bennett, Jean; Sun, Junwei & Shindler, Kenneth et al., "Gene therapy for ocular disorders", published 2018-11-01, assigned to The Trustees of the University of Pennsylvania
  29. ↑ WO application 2010088259, Borghuis, Bart; Letterio, Fred & Bennett, Jean, "Syringe actuator", published 2010-08-05, assigned to The Trustees of the University of Pennsylvania & inventors
  30. ↑ US application 2019151473, Bennett, Jean; Sun, Junwei & Vasireddy, Vidyullatha, "Methods and compositions for treatment of disorders and diseases involving RDH12", published 2019-05-23, assigned to The Trustees of the University of Pennsylvania
  31. ↑ WO application 2018160849, Bennett, Jean; Bennicelli, Jeannette & Sun, Junwei et al., "Gene therapy for ocular disorders", published 2018-09-07, assigned to The Trustees of the University of Pennsylvania
  32. ↑ US 10266845, Cronin, Therese; Bennett, Jean & Vandenberghe, Luk E., "Enhanced AAV-mediated gene transfer for retinal therapies", published 2019-04-23, assigned to The Trustees of the University of Pennsylvania
  33. ↑ US 10668129, Leveillard, Thierry; Flannery, John & Mei, Xin et al., "Synergistic combination of neuronal viability factors and uses thereof", published 2020-06-02, assigned to Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, The Regents of the University of California & The Trustees of the University of Pennsylvania
  34. ↑ US 20150374851, Lipschutz, Joshua H.; Bennett, Jean & Chung, Daniel C., "AAV vectors expressing Sec10 for treating kidney damage", published 2015-12-31, assigned to The Trustees of the University of Pennsylvania
  35. ↑ US 10857240, Bennicelli, Jeannette; Bennett, Jean & Sun, Junwei, "Methods and compositions for treatment of ocular disorders and blinding diseases", published 2020-12-08, assigned to The Trustees of the University of Pennsylvania
  36. ↑ US 10448823, High, Katherine A.; Bennett, Jean & Chung, Daniel et al., "Apparatus and methods for testing visual function and functional vision at varying luminance levels", published 2019-10-22, assigned to The Children's Hospital of Philadelphia and The Trustees of the University of Pennsylvania
  37. ↑ US 10987433, Bennett, Jean; Bennicelli, Jeannette & Dooley, Scott J. et al., "Compositions and methods for Correction of Heritable Ocular Disease", published 2021-04-27, assigned to The Trustees of the University of Pennsylvania and Lloyd G. Mitchell
  38. ↑ US 11206977, Bennett, Jean, "Vision test for determining retinal disease progression", published 2021-12-28, assigned to The Trustees of the University of Pennsylvania
  39. ↑ US 10392622, Lewis, Mitchell; Bennett, Jean & Vandenberghe, Luk et al., "Compositions and methods for self-regulated inducible gene expression", published 2019-08-27, assigned to The Trustees of the University of Pennsylvania
  40. ↑ WO application 2009134681, Wilson, James M.; Vandenberghe, Luc H. & Bennett, Jean et al., "AAV7 viral vectors for targeted delivery of RPE cells", published 2009-11-05, assigned to The Trustees of the University of Pennsylvania and Smithkline Beecham Corp. & inventors
  41. ↑ US 10696983, Bennett, Jean & Lipschutz, Joshua, "method for transducing cells with primary cilia", published 2020-06-30, assigned to The Trustees of the University of Pennsylvania and inventors
  42. ↑ US 10155794, Drivas, Theodore G. & Bennett, Jean, "Compositions and methods for treatment of disorders related to CEP290", published 2018-12-18, assigned to The Trustees of the University of Pennsylvania
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