Biomedical engineer
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
^
"2022 NAS Election" .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^ 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 .
^
"Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award" . Smithsonian Magazine . Retrieved 2020-01-31 .
^
"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 .
^
"Pioneer in Ocular Gene Therapy to Receive 2018 Marion Spencer Fay Award" . DrexelNow . 2018-09-14. Retrieved 2020-02-01 .
^
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.
^
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
^
US 2003003582 , Wakefield, John & Bennett, Jean, "Trans-viral vector mediated gene transfer to the retina", issued 2003-01-02, assigned to Tranzyme Inc.
^
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
^
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
^
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.
^
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
^
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
^
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.
^
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
^
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
^
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
^
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
^
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
^
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
^
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
^
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
^
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
^
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
^
US 11206977 , Bennett, Jean, "Vision test for determining retinal disease progression", published 2021-12-28, assigned to
The Trustees of the University of Pennsylvania
^
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
^
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
^
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
^
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
International National Academics