Oral delivery of angiotensin converting enzyme 2 (ACE2) or angiotensin-(1-7)-bioencapsulated in plant cells attenuates pulmonary hypertension, cardiac dysfunction and development of autoimmune and experimentally induced ocular disorders

US12059454B2 · kind B2 · utility

Assignees

• The Trustees of the University of Pennsylvania · US
• University of Florida Research Foundation, INC. · US

Inventors

• Henry Daniell · Media, US
• Qiuhong Li · Gainesville, US
• Mohan K. Raizada · Alachua, US

Key dates

• Filing date: Feb 2, 2022
• Grant date: Aug 13, 2024
• Expiry date: Feb 2, 2042

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Emerging evidence indicates that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin converting enzyme2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to pulmonary hypertension (PH). However, clinical success for long-term delivery of ACE2 or Ang-(1-7) would require stability and ease of administration to increase patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect from acids and gastric enzymes; fusion to a transmucosal carrier facilitates effective systemic absorption. Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) attenuated monocrotaline (MCT)-induced increase in right ventricular systolic pressure, decreased pulmonary vessel wall thickness and improved right heart function in both prevention and reversal protocols. Furthermore, combination of ACE2 and Ang-(1-7) augmented the beneficial effects against cardio-pulmonary pathophysiology induced by MCT administration.Experiments have also been performed which indicate that this approach is also suitable for the treatment or inhibition of experimental uveitis and a…