Henry Daniell, Ph.D.

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Professor of Biochemistry
Department: Biochemistry

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, Nair SK, Esmaeili N, Wakade G, Shahid N, Ganesan PK, Islam R, Shepley-Mctaggart A, Feng S, Gary EN, Ali AR, Nuth M, Cruz SN, Graham-Wooten J, Streatfield SJ, Montoya-Lopez R, Kaznica P, Mawson M, Green BJ, Ricciardi R, Milone M, Harty RN, Wang P, Weiner DB, Margulies KB, Collman RG: Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection. Molecular Therapy 30: 1966-1978 2022.

Daniell H, Nair SK, Guan H, Guo Y, Kulchar RJ, Torres MDT, Shahed-Al-Mahmud Md, Wakade G, Liu YM, Marques A, Graham-Wooten J, Zhou W, Wang P, Molugu SK, de Araujo WR, de la Fuente-Nunez C, Ma C, Short WR, Tebas P, Margulies KB, Bushman FD, Mante FK, Ricciardi R, Collman RG, Wolff MS : Debulking different Corona (SARS-COV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission. Biomaterials 288 (2022) 121671 288: 121671, 2022.

Daniell H, Nair SK, Shi Y, Wang P, Montone KT, Shaw PA, Choi GH, Ghani D, Weaver J, Rader DJ, Margulies KB, Collman RG, Laudanski K, Bar KJ : Decrease in Angiotensin Converting Enzyme 2 activity but not concentration in plasma/lungs in COVID-19 patients – offers clues for diagnosis/treatment. Molecular Therapy: Methods & Clinical Development 26: 309-322 26, 2022.

Singh R, Lin S, Nair SN, Shi Y, Daniell H : Oral booster vaccine antigen – expression of full length SARS-CoV-2 spike protein in lettuce chloroplasts. Plant Biotechnology Journal https://doi.org/10.1111/pbi.13993 2022.

Srinivasan A, Herzog RW, Khan I, Sherman A, Bertolini T, Wynn T, Daniell H : Preclinical development of plant based oral immunomodulatory therapy for hemophilia B. Plant Biotechnology Journal 19: 1952-1966. 2021.

Singh R, Ren Z, Shi Y, Lin S, Kwon KC, Balamurugan S, Rai V, Mante F, Koo H, Daniell H: Affordable oral health care: dental biofilm disruption using chloroplast made enzymes with chewing gum delivery. Plant Biotechnology Journal 19: 2113-2125 2021.

Park J, Yan G, Kwon KC, Lui M, Gonnella PA, Yang S, Daniell H: Oral delivery of novel human IGF-1 bioencapsulated in lettuce cells promotes musculoskeletal cell proliferation, differentiation and diabetic fracture healing. Biomaterials 233:119591 2020.

Daniell H, Mangu V, Yakubov B, Park J, Habibi P, Shi Y, Gonnella PA, Fisher A, Cook T, Zeng L, Kawut SM, Lahm T : Investigational new drug enabling angiotensin oral delivery studies to attenuate pulmonary hypertension. Biomaterials 233: 119750 2020.

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.

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

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Last updated: 01/15/2023
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