University of Pennsylvania

Auburn University

University of Florida Research Foundation Inc

University of Central Florida Research Foundation Inc

Other

Herzog, Roland W.

Daniell, Henry

Henry Daniell

Bruce A McFadden

Qiuhong Li

Mohan Raizada

Roland W Herzog

Hyun Koo

William Moar

Mohan K Raizada

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

Methods for improving transgene in chloroplasts are disclosed along with improved transgenes so produced and methods of use thereof for the treatment of disease. Specifically, the methods comprising analyzing the native sequence of a nucleic acid encoding a protein of interest and replacing codons in said sequence with those preferentially used in psbA genes in chloroplasts in higher plants.

Codon optimization for increasing transgene expression in chloroplasts of higher seed plants

The invention provides a method for combating biofilm, said method comprising contacting a biofilm with a composition comprising an effective amount of antimicrobial peptide biofilm enzyme combinations, preferably in the form of a fusion protein. The biofilm may be on an animate or inanimate surface and both medical and non-medical uses and methods are provided. In one aspect the invention provides a composition for use in the treatment or prevention of a biofilm in a subject, particularly in the oral cavity.

Compositions and methods for inhibiting biofilm deposition and production

Compositions and methods effective to provide therapeutic benefit for disorders of the central nervous system via oral or systemic delivery of therapeutic proteins produced in plastids are disclosed.

Compositions and methods for delivery of bioencapsulated proteins across blood-brain and retinal barriers

Compositions and methods for down-regulating genes through oral administration of RNAi molecule encapsulated in plant cells are provided.

Compositions and methods thereof for down-regulation of genes following oral delivery of an RNAi molecule bioencapsulated within plant cells

Disclosed herein are compositions and methods for treating Type II diabetes. The compositions comprise plant expressed Exendin 4. Particularly exemplified are plant derived compositions that include a CTB-EX4 conjugate that is bioencapsulated in chloroplasts.

Orally administered plastid expressed cholera toxin B subunit-exendin 4 as treatment for type 2 diabetes

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

Disclosed herein are compositions for conferring oral tolerance in mammals to autoimmune disorders such as diabetes, as well as vectors and methods for plastid transformation of plants to produce a CTB-Pins protein for oral delivery. The invention also extends to the transformed plants, plant parts, and seeds and progeny thereof. The invention is applicable to plants edible without torrefying. Exemplified herein is the stable transformation ofsuch that CTB-Pins is expressed.

Chloroplasts engineered to express pharmaceutical proteins in edible plants

Disclosed herein are materials useful for degrading plant biomass material. In exemplary embodiments, the plant material comprises one or more enzymes that are expressed in plants and/or bacteria. Specifically exemplified herein are plant degrading enzymes expressed in chloroplasts. The chloroplast expressed enzymes may be provided as cocktails for use in conjunction with conventional methods of converting biomass into biofuels, such as cellulosic ethanol. In other exemplary embodiments, methods and materials are disclosed for degrading mannans.

Expression of &#x3b2;-mannanase in chloroplasts and its utilization in lignocellulosic woody biomass hydrolysis

Disclosed herein are materials useful for degrading plant biomass material. In exemplary embodiments, the plant material comprises one or more enzymes that are expressed in plants and/or bacteria. Specifically exemplified herein are plant degrading enzymes expressed in chloroplasts. The chloroplast expressed enzymes may be provided as cocktails for use in conjunction with conventional methods of converting biomass into biofuels, such as cellulosic ethanol.

Production and use of plant degrading materials

Protein replacement therapy for patients with hemophilia or other inherited protein deficiencies is often complicated by pathogenic antibody responses, including antibodies that neutralize the therapeutic protein or that predispose to potentially life-threatening anaphylactic reactions by formation of IgE. Using murine and canine hemophilia as a model, we have developed a prophylactic protocol against such responses that is non-invasive and does not include immune suppression or genetic manipulation of the patient's cells. Oral delivery of a coagulation factor expressed in chloroplasts, bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies in protein replacement therapy. Inhibitor titers were mostly undetectable and up to 100-fold lower in treated subjects when compared to controls. Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous coagulation factor protein. Finally, the method can effectively be used to reverse or reduce undesirable pre-existing inhibitor titers.

Compositions and methods for suppression of inhibitor formation against coagulation factors in hemophilia patients

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

Vaccines for conferring immunity in mammals to infective pathogens are provided, as well as vectors and methods for plastid transformation of plants to produce protective antigens and vaccines for oral delivery. The vaccines are operative by parenteral administration as well. The invention also extends to the transformed plants, plant parts, and seeds and progeny thereof. The invention is applicable to monocot and dicot plants.

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Media, PA, United States of America

Henry Daniell