University of Florida Research Foundation Inc

University of Pennsylvania

Qiuhong Li

Alfred Samuel Lewin

Cristhian J Ildefonso

Mohan Raizada

Henry Daniell

William W Hauswirth

Mohan K Raizada

The present invention provides methods and compositions for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, ocular neovascularization, or ocular inflammation. In an exemplary embodiment, a method is disclosed that involves administering an expression vector that delivers a secretable and cell penetrating CARD to a subject in need of treatment or prevention of age-related macular degeneration or another condition involving macular degeneration or ocular neovascularization.

Delivery of card protein as therapy for occular inflammation

The present invention provides methods and compositions for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, ocular neovascularization, or inflammation, including ocular inflammation. In some embodiments, the methods comprise administering an expression vector that delivers a secretable and cell penetrating Nrf2 to a subject in need thereof.

Delivery of NRF2 as therapy for protection against reactive oxygen species

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.

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

Provided herein are polynucleic acids and expression vectors for the expression and secretion of angiotensin peptide fragments (e.g., angiotensin-(1-7)) in probiotic bacteria. Provided herein are also probiotic compositions that enable efficient, cost-effective and patient friendly oral therapeutics for treating diverse pathological conditions that involve the renin-angiotensin system (RAS), e.g., pulmonary hypertension, diabetes, diabetic complications, cardiovascular diseases, and ocular inflammatory and neurodegenerative diseases.

Genetically modified probiotics for oral delivery of renin-angiotensin related therapeutic proteins and peptides

Delivery of card protein as therapy for ocular inflammation

The present invention is directed to a delivery vector for transferring a small peptide coding sequence to a cell for expression of the small peptide coding sequence within the cell. The delivery vector comprises a secretory signal sequence; a sequence encoding a carrier protein operatively associated with the secretory signal sequence; a sequence encoding a cleavage site operatively associated with the sequence encoding a carrier protein; and a sequence encoding a small peptide operatively associated with the sequence encoding a cleavage site.

Small angiotensin peptide expression system in mammalian cells

Delivery of Nrf2 as therapy for protection against reactive oxygen species

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 experimental induced ocular disorders

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Gainesville, FL, United States of America

Qiuhong Li