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 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).

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. Oral delivery of angiotensin converting enzyme 2 (ACE2) or angiotensin-(1-7) attenuated pulmonary hypertension and associated cardiac dysfunction. 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.

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:

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)

Synthetic biology / synplastome (funded by DOE - ARPA-E 2012-2020)

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

Lab personnel:

Dr. Henry Daniell, Professor and director of Translational Research

Dr. Kwang-Chul Kwon, senior pos-doctoral fellow

Dr. Bei Zhang,Research Associate

Dr. Jiyoung Park, Research Associate

Dr. Balamurugan Shanmugaraj, Research Associate

Dr. Prasanjit Saha, Senior Research Associate

Dr. Venkata Mangu, Senior post-doctoral fellow

Dr. Shiv Verma, Senior Research Associate

Dr. Yihe Yu, Senior Research Associate

Ms. Shina Lin, M.S., Research Associate

Ms. Wan Jung Chang, M.S., graduate student

Selected Publications

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, 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.

Shahid N, Daniell H: Plant‐based oral vaccines against zoonotic and non‐zoonotic diseases. Plant Biotechnology Journal 14: 2079-2099, 2016.

Daniell H, Lin CS, Yu M, Chang WC : Chloroplast genomes: Diversity, evolution and applications in genetic engineering. Genome Biology 17: 134, 2016.

Malhotra K, Subramaniyan M, Rawat K, Kalamuddin M, Qureshi MI, Malhotra P, Mohmmed A, Katrina Cornish K, Daniell H, Kumar S : Compartmentalized metabolic engineering for artemisinin biosynthesis and effective malaria treatment by oral delivery of plant cells. Molecular Plant 9: 1464-1477, 2016.

Xiao Y, Kwon KC, Hoffman BE, Kamesh A, Jones NT, Herzog RW and Daniell H: Low cost delivery of proteins bioencapsulated in plant cells to human non-immune or immune modulatory cells. Biomaterials 80: 68-79, 2016.

Pasoreck EK, Su J, Silverman IM, Gosai SJ, Gregory BD, Yuan JS, Daniell H: Terpene metabolic engineering via nuclear or chloroplast genome profoundly and globally impacts off target pathways through metabolite signaling. Plant Biotechnology Journal 14: 1862-1875, 2016.

Liu Y, Kamesh AC, Xiao Y, Sun V, Hayes M, Daniell H, Koo H.: Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells. Biomaterials 105: 156-166, 2016.

Chan HT, Xiao Y, Weldon WC, Oberste SM, Chumakov K, Daniell H: Cold chain and virus free chloroplast made booster vaccine to confer immunity against different polio virus serotypes. Plant Biotechnology Journal 14: 2190-2200, 2016.

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Last updated: 01/18/2017
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