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 autoimmune uveoretinitis These studies provide proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7)
delivery system using transplastomic technology for pulmonary and
ocular disease therapeutics.