Jean Bennett Explained

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

Notes and References

  1. Web site: 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. 10.1089/hum.2014.2529. 1043-0342. 4137328. 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. 10.1038/nm0696-649. 1078-8956. 8640555. 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. 0146-0404. 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. 10.1073/pnas.96.17.9920. 0027-8424. 10449795. 22311. 1999PNAS...96.9920B. free .
  6. Book: Bennett. J.. Anand. V.. Acland. G. M.. Maguire. A. M.. Cross-species comparison of in vivo reporter gene expression after recombinant adeno-associated virus-mediated retinal transduction . 2000. Vertebrate Phototransduction and the Visual Cycle, Part B. Methods in Enzymology. 316. 777–789. 10.1016/s0076-6879(00)16762-x. 0076-6879. 10800714. 978-0-12-182217-0 .
  7. News: Patient Dies During a Trial Of Therapy Using Genes. Wade. Nicholas. 1999-09-29. The New York Times. 2020-02-01. en-US. 0362-4331.
  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. 10.1038/ng0501-92. 1061-4036. 11326284. 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. 10.1056/NEJMoa0802315. 1533-4406. 2829748. 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. 10.1016/S0140-6736(09)61836-5. 1474-547X. 4492302. 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. 10.1073/pnas.0807027105. 1091-6490. 2567501. 18809924. 2008PNAS..10515112C. free .
  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. 10.1056/NEJMoa0802268. 1533-4406. 18441371. 10261/271174. free.
  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. en. 10. 1. 427. 10.1038/s41467-018-08243-1. 30683875. 6347594. 2019NatCo..10..427I. 2041-1723.
  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. en. 13. 380–389. 10.1016/j.omtm.2019.03.004. 31024980. 6477656. 2329-0501. free.
  15. 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. Duong. Thu T.. Lim. James. 2019. Stem Cells International. en. Vasireddy. Vidyullatha. Papp. Tyler. Nguyen. Hung. Leo. Lanfranco. Pan. Jieyan. Zhou. Shangzhen. Chen. H. Isaac. 2019 . 1–11 . 10.1155/2019/7281912 . 30800164 . 6360060 . free .
  16. Web site: Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award. Smithsonian Magazine. en. 2020-01-31.
  17. Web site: Three Penn Medicine Gene Therapy Innovators Receive International Award for Pioneering Work to Treat Childhood Blindness – PR News. www.pennmedicine.org. en-US. 2020-02-01.
  18. Web site: Pioneer in Ocular Gene Therapy to Receive 2018 Marion Spencer Fay Award. 2018-09-14. DrexelNow. en. 2020-02-01.
  19. Method of treating or retarding the development of blindness. 2012-04-03. US. 8147823. The Trustees of the University of Pennsylvania, University of Florida Research Foundation Inc.. Cornell Research Foundation Inc.. Acland. Gregory M.. Aguirre. Gustavo D.. Bennett. Jean. William W. Hauswirth;Samuel G. Jacobson;Albert M. Maguire.
  20. Methods, systems, and computer readable media for testing visual function using virtual mobility tests. 2019-10-31. application. WO. 2019210087. The Trustees of the University of Pennsylvania. Bennett. Jean. Aleman. Tomas S.. Ashtari. Manzar. Alexander Jacob Miller;Nancy Bennett.
  21. Trans-viral vector mediated gene transfer to the retina. 2003-01-02. US. 2003003582. Tranzyme Inc.. Wakefield. John. Bennett. Jean.
  22. Modified AAV8 capsid for gene transfer for retinal therapies. 2015-12-16. EP. 2954051. The Trustees of the University of Pennsylvania. Cronin. Therese. Bennett. Jean. Vandenberghe. Luk E..
  23. Proviral plasmids and production of recombinant adeno-associated virus. 2016-02-02. US. 9249425. The Trustees of the University of Pennsylvania & inventors. Bennett. Jean. Bennicelli. Jeannette L..
  24. Method of treating or retarding the development of blindness. 2002-10-24. WO. 02082904. The Trustees of the University of Pennsylvania, University of Florida Research Foundation Inc.. Cornell Research Foundation Inc.. Acland. Gregory M.. Aguirre. Gustavo D.. Bennett. Jean. William W. Hauswirth;Samuel G. Jacobson;Albert M. Maguire.
  25. Gene therapy for ocular disorders. 2018-12-20. WO. 2018232149. application. The Trustees of the University of Pennsylvania. Bennett. Jean. Sun. Junwei. Bennicelli. Jeannette.
  26. Gene therapy for treating peroxisomal disorders. 2018-12-06. WO. 2018218359. application. The Trustees of the University of Pennsylvania, the inventors, Nancy Braverman,Catherine Argyriou and Joseph Hacia. Bennett. Jean. Sun. Junwei. Song. Ji Yun. Devin McDougald.
  27. Trans-splicing molecules. 2019-04-17. WO. 2019204514. application. The Trustees of the University of Pennsylvania. Limelight Bio Inc.. Johnson. Philip R.. SCchnepp. Bruce C.. Bennett. Jean. Scott J. Dooley;Krishna Jawaharlal Fisher;Junwei Sun.
  28. Gene therapy for ocular disorders. 2018-11-01. WO. 2018200542. The Trustees of the University of Pennsylvania. Bennett. Jean. Sun. Junwei. Shindler. Kenneth. McDougald. Devin. application.
  29. Syringe actuator. 2010-08-05. WO. 2010088259. application. The Trustees of the University of Pennsylvania & inventors. Borghuis. Bart. Letterio. Fred. Bennett. Jean.
  30. Methods and compositions for treatment of disorders and diseases involving RDH12. 2019-05-23. US. 2019151473. application. The Trustees of the University of Pennsylvania. Bennett. Jean. Sun. Junwei. Vasireddy. Vidyullatha.
  31. Gene therapy for ocular disorders. 2018-09-07. WO. 2018160849. application. The Trustees of the University of Pennsylvania. Bennett. Jean. Bennicelli. Jeannette. Sun. Junwei . Ji-yun Song;Sergei Nikonov.
  32. Enhanced AAV-mediated gene transfer for retinal therapies. 2019-04-23. US. 10266845. The Trustees of the University of Pennsylvania. Cronin. Therese. Bennett. Jean. Vandenberghe. Luk E..
  33. Synergistic combination of neuronal viability factors and uses thereof. 2020-06-02. US. 10668129. 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. Leveillard. Thierry. Flannery. John. Mei. Xin. Leah Byrne;José-Alain Sahel;Emmanuelle Clerin-Lachapelle;Junwei Sun;Jean Bennett;Jeannette .
  34. AAV vectors expressing Sec10 for treating kidney damage. 2015-12-31. US. 20150374851. The Trustees of the University of Pennsylvania. Lipschutz. Joshua H.. Bennett. Jean. Chung. Daniel C..
  35. Methods and compositions for treatment of ocular disorders and blinding diseases. 2020-12-08. US. 10857240. The Trustees of the University of Pennsylvania. Bennicelli. Jeannette. Bennett. Jean. Sun. Junwei.
  36. Apparatus and methods for testing visual function and functional vision at varying luminance levels. 2019-10-22. US. 10448823. The Children's Hospital of Philadelphia. The Trustees of the University of Pennsylvania. High. Katherine A.. Bennett. Jean. Chung. Daniel. Albert Maguire;Jennifer Wellman;Sarah McCague;Gregory Podsakoff.
  37. Compositions and methods for Correction of Heritable Ocular Disease. 2021-04-27. US. 10987433. The Trustees of the University of Pennsylvania. Lloyd G. Mitchell. Bennett. Jean. Bennicelli. Jeannette. Dooley. Scott J.. Mitchell. Lloyd G..
  38. Vision test for determining retinal disease progression. 2021-12-28. US. 11206977. The Trustees of the University of Pennsylvania. Bennett. Jean.
  39. Compositions and methods for self-regulated inducible gene expression. 2019-08-27. US. 10392622. The Trustees of the University of Pennsylvania. Lewis. Mitchell. Bennett. Jean. Vandenberghe. Luk. Matthew Sochor;Theodore G. Drivas.
  40. AAV7 viral vectors for targeted delivery of RPE cells. 2009-11-05. WO. 2009134681. application. The Trustees of the University of Pennsylvania. Smithkline Beecham Corp. & inventors. Wilson. James M.. Vandenberghe. Luc H.. Bennett. Jean. Karen Kozarsky;Peter Ertl.
  41. method for transducing cells with primary cilia. 2020-06-30. US. 10696983. The Trustees of the University of Pennsylvania. inventors. Bennett. Jean. Lipschutz. Joshua.
  42. Compositions and methods for treatment of disorders related to CEP290. 2018-12-18. US. 10155794. The Trustees of the University of Pennsylvania. Drivas. Theodore G.. Bennett. Jean.

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