Use of functional recombinant ACE2 and Angiotensin-(1-7) proteins to improve the clinical course of patients with symptomatic COVID-19 infection.
COVID-19 is associated with high rates of respiratory failure, cardiac injury and death. Patients suffering from COVID-19 generally present with reduced expression of angiotensin converting enzyme 2 (ACE2) and depletion of ACE2’s protein product, the anti-inflammatory peptide Angiotensin-(1-7). This down-regulation of ACE2 expression is induced by viral invasion of SARS-CoV-2, the virus causing COVID-19 disease. Decreased ACE2 expression has been linked to acute respiratory distress, severe lung injury, multi-organ failure and death, especially in older patients.
As a potential treatment for the severe complications of COVID-19 disease, oral supplementation of ACE2 and Angiotensin-(1-7) are being tested in a clinical trial to determine whether this intervention elicits protective effects on cardiac and respiratory function in COVID-19 patents. Restoring ACE2 with this therapeutic may mitigate virus-mediated lung and cardiac injury in COVID-19 patients.
Dr. Daniell and colleagues have developed a platform for producing recombinant ACE2 and Angiotensin-(1-7) in lettuce plants that is shelf-stable. Preclinical studies in pulmonary hypertension animal models showed that orally delivered ACE2 made in plant cells accumulated ten times higher in the lungs than in the blood and treated pulmonary hypertension at doses without any toxic effects. This application of plant-derived ACE2 therapy to patients with COVID-19 infection is enabled, in part, by prior toxicology studies done at Stanford Research Institute funded by NIH SMARTT program. The fact that freeze-dried plant cells can be stored at ambient temperature for one year and can be taken at home by COVID-19 patients are other attractive features of this novel approach.
- Low-cost delivery compared to traditional protein therapies and/or gene therapies
- Potential for reducing the use of high-cost, high-demand medical supplies such as ventilators
- Treatment for lung injury caused by COVID-19 disease
Oral ACE2 and Ang(1-7) Supplementation In Symptomatic COronaVIrus Disease (The OAASIS COVID trial): Background information on application of invention to COVID-19 patients.
Angiotensin Converting Enzyme 2 (ACE2) is the binding site for SARS-CoV-2 entry into the lungs.
Downregulation of ACE2 by SARS-CoV-2 leads to excess Ang II (pro-inflammatory) and reduced Ang (1-7) (anti-inflammatory)
Intervention: Supplement ACE2 and Ang(1-7) with an orally-delivered plant-based formulation to debulk SARS-CoV2 and restore a more favorable balance of AngII and Ang(1-7)
Stage of Development:
Therapeutics: Phase I/II clinical trial
- Daniell et al. Biomaterials, 2020, 233
- Penn Dental Med Website. Spotlight on Penn’s Vagelos LSM Capstone Course, 2018.
- Kwon, K. Plant Biotech J, 2015, 13 -1017
- Shenoy et al. Hypertension, 2014, 64 - 1248
- Shil et al. Molec Ther, 2014, 22(12) - 2069
- Penn Today 5.5.20