Henry Daniell, Ph.D.

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Professor of Biochemistry
Department: Biochemistry
Graduate Group Affiliations

Contact information
547 Levy, 240 south 40th Street
Philadelphia, PA 19104-6030
Office: 1-215-746-2563
Fax: 1-215-898-3695
BS (Botany/Chemistry)
University of Madras, 1969.
MS (Botany)
University of Madras, 1971.
PhD (Biochemistry)
Madurai Kamaraj University, 1980.
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Description of Research Expertise

Research Interests: Oral delivery of human therapeutic proteins bio-encapsulated within plant cells to confer protection against inherited or infectious diseases

Key Words: Oral delivery, bioencapsulation of biopharmaceuticals in plant cells, vaccine antigens, autoimmune disorders, infectious diseases or metabolic disorders

In an emerging new concept, freeze-dried plant cells (lettuce) expressing biopharmaceuticals (fused with transmucosal carriers) are protected in the stomach from acids/enzymes but are released to the circulatory or immune system when plant cell walls are digested by microbes that colonize the gut. Therapeutic proteins in lyophilized plant cells (in capsules) are stable >30 months at room temperature and maintain their folding, disulfide bonds, assembly and functionality.

Oral delivery of antigens or auto-antigens bio-encapsulated in plant cells:Several vaccine antigens (against Dengue, polio, malaria, tuberculosis, cholera, anthrax, plague, etc) or autoantigens (diabetes, hemophilia, etc) have been expressed in lettuce chloroplasts. Vaccine antigens bio-encapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. In recent studies (2019 publications) supported by the Gates Foundation were done in collaboration with FDA and neutralization studies were evaluated by the CDC laboratories.

Oral delivery of blood clotting factors FVIII or FIX prevented inhibitory antibodies/complications after injection of blood clotting factors in hemophilia A/B mice or dogs by developing tolerance. In-planta drug dose was determined using cutting edge proteomic approaches and in collaboration with industry (Novo Nordisk, Bayer, Sire/Takeda). NIH SMARTT program funds IND enabling third party toxicology, pharmacokinetic and pharmaodynamic studies performed at Staanford Research Institute to advance products to the clinic.

Oral delivery of functional proteins: Oral delivery of exendin-4 expressed in plant cells regulated blood glucose levels similar to injections by stimulating insulin secretion and a 5,000 fold excess dose didn’t cause hypoglycemia because insulinotropism of exendin-4 is glucose dependent. Amyloid plaques were reduced in vivo by 70% in hippocampus and cortex brain regions when fed with myelin basic protein and reduced Aβ42 accumulation in retinae and prevented loss of retinal ganglion cells in 3xTg Alzheimer’s disease mice. Oral delivery of angiotensin converting enzyme (Ace2) and angiotensin1-7 attenuates pulmonary hypertension and cardiac dysfunction and heart failure. NIH SMARTT program is advancing these drugs to the clinic (2020 publication).

Therefore, this new platform should offer a low cost alternative to deliver human therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections.

Rotation projects:

Suppression of antibodies developed in gene therapy by oral delivery of antigens
Oral polio booster vaccine (funded by the Bill and Melinda Gates Foundation)
Oral immune modulatory therapy using antigens bio-encapsulated in plant cells (funded by the NIH R01 grants 2010-2022)
Oral delivery of functional blood proteins (funded by NIH R01 2002 - 2022)
Mechanistic studies on immunity or tolerance using antigens/auto-antigens (funded by the NIH 2010-2022)

Topical drug delivery (funded by Johnson & Johnson, 2016 - 2018)

Lab personnel:

Dr. Henry Daniell, W.D. Miller Professor, Director of Translational Research

Dr. Jiyoung Park, post-doctoral fellow

Dr. Prasanjit Saha, Senior Research Associate

Dr. Venkata Mangu, Senior post-doctoral fellow

Dr. Rahul Singh, post-doctoral fellow

Dr. Bin Yi, Senior Research Associate

Dr. Dongli He, Senior Research Associate

Dr. Patricia Gonnella, Research Faculty

Dr. Yao Shi, post-doctoral fellow

Dr. Dr. Peyman Habibi, post-doctoral fellow

Dr. Imran Kahn, post-doctoral fellow

Dr. Uma Kumari, post-doctoral fellow

Dr. Aparajithe Srinivasan, Research Associate

Dr. Smruti Nair, DScD student - 2019 fall

Selected Publications

Daniell H, M. Kulis M, Herzog RW: Plant cell-made protein antigens for induction of oral tolerance Plant cell-made protein antigens for induction of oral tolerance. Biotechnology Advances, doi.org/10.1016/j.biotechadv.2019.06.012 2019.

Park J, Yan G, Kwon KC, LiuM, Gonnella PA, Yang S, Daniell H: Oral delivery of human IGF1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing. https://www.sciencedirect.com/science/article/pii/S0142961219306908?via%3Dihub 2019.

Daniell H, Rai V, Xiao Y: Cold-chain and virus free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes. Plant Biotechnology Journal 17: 1357 - 1368 2019.

Kumari U, Singh R, Ray T, Rana S, Saha P, Malhotra K, Daniell H : Validation of leaf enzymes in the detergent and textile industries: launching of a new platform technology. Plant Biotechnology Journal 17: 1167-1182. 2019.

Kwon K-C, Sherman A, Chang W-J, Kamesh A, Biswas M, Herzog RW, Daniell H : Expression and assembly of largest foreign protein in chloroplasts: oral delivery of human FVIII made in lettuce chloroplasts robustly suppresses inhibitor formation in hemophilia A mice. Plant Biotechnology Journal 16: 1148-1160 2018.

Herzog RW, Nichols TC, Su J, Zhang B, Sherman A, Merricks EP, Raymer R, Perrin GQ, Hager M, Wiinberg B, Daniell, H.: Oral Tolerance Induction in Hemophilia B Dogs Fed with Transplastomic Lettuce. Molecular Therapy 25, January 2017.

Daniell H, Lin CS, Yu M, Chang WC : Chloroplast genomes: Diversity, evolution and applications in genetic engineering. Genome Biology 17: 134 2017.

Daniell H, Chan HT, Pasoreck EK: Vaccination through chloroplast genetics: Affordable protein drugs for the prevention and treatment of inherited or infectious diseases. Annual Review of Genetics 50: 595-618, December 2016.

Kwang-Chul Kwon, Henry Daniell : Oral delivery of protein drugs bioencalsulated in plant cells. Molecular Therapy 24: 1342-1350, August 2016.

Wang, X, Su, J, Sherman, A, Rogers, GL, Liao, G, Hoffman, BE, Leong, KW, Terhorst, C, Daniell, H, and Herzog, RW. : Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+ CD4+ T cells. Blood 125: 2418-2427, 2015.

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Last updated: 12/25/2019
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