Entity

Time filter

Source Type

State University, AR, United States

The current invention involves the use of protein lectins produced by plants including the non-toxic carbohydrate binding subunits (B subunits) of plant AB toxins (PTB lectins) as delivery vehicles for mobilizing associated drug substances for delivery to animal and human cells. The resulting protein fusions or conjugates retain lectin carbohydrate specificity for binding to cells and cellular trafficking activity so as to deliver an associated drug compound to the site of disease manifestation. One embodiment of this invention concerns the ability of ricin toxin B subunit, as a model PTB lectin, to deliver enzyme replacement therapeutic drugs to cells of several organs of the body including the brain and central nervous system, eyes, ears, lungs, bone, heart, kidney, liver, and spleen for treating lysosomal diseases.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 90.00K | Year: 2010

As the nation attempts to meet the challenges posed by the spread of pandemic influenza there is a need for innovative strategies to produce effective vaccines for humans, poultry and livestock. Interleukin-12 (IL-12) is a potent adjuvant of cell-mediated immunity that has been shown to enhance protection afforded by influenza vaccines. The use of IL-12 adjuvant could improve vaccines for several serious porcine diseases including flu but the high cost of current production methods does not sustain the scaled up product availability necessary for large scale vaccination strategies. Plant-based production offers several potential benefits over conventional production systems including lower startup costs and increased flexibility in terms of scale-up, storage, safety, and cost containment. We have demonstrated that plants can produce fully functional mouse and chicken IL-12 at production levels compatible with large scale commercial applications. This Phase I SBIR proposes to show the feasibility of plant-based bio-production of porcine IL-12 (PoIL-12) by addressing the following specific aims: I. Construct porcine IL-12 gene vectors for expression in plants. II. Test IL-12 gene vectors for protein yield and bioactivity in a tobacco transient expression system. This Phase I feasibility study will establish the ability of plants to produce bioactive porcine IL-12, provide productivity assessments, and establish bio-production protocols for supplying bioactive PoIL-12 to researchers for further R&D. Phase II research will address development of stable transgenic plant lines, IL-12 product characterization and purification, scaled up production, and demonstrations of adjuvancy and protection against flu in porcine vaccine trials.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

DESCRIPTION (provided by applicant): The goal of this proposal is to develop an effective enzyme replacement therapy (ERT) for patients suffering from GM1 Gangliosidosis by integrating a novel protein fusion ERT cell delivery strategy under development atBioStrategies LC and by exploiting safety, supply, and cost advantages of new plant-based enzyme therapeutics bio-manufacturing systems. GM1 Gangliosidosis is a rare genetic lysosomal storage disorder affecting less than 200,000 people in the U.S. It is caused by a defect in the gene encoding the enzyme ?-galactosidase and is characterized by progressive degeneration of normal childhood development especially in brain function leading to death at an early age. Current treatment options are limited to management of disease symptoms and development of an effective ERT drug has been hindered by challenges of delivering these drugs to the brain and central nervous system. This research project is a collaboration between BioStrategies LC, a company focused


The current invention involves the use of protein lectins produced by plants including the non-toxic carbohydrate binding subunits (B subunits) of plant AB toxins (PTB lectins) as delivery vehicles for mobilizing associated drug substances for delivery to animal and human cells. The resulting protein fusions or conjugates retain lectin carbohydrate specificity for binding to cells and cellular trafficking activity so as to deliver an associated drug compound to the site of disease manifestation. One embodiment of this invention concerns the ability of ricin toxin B subunit, as a model PTB lectin, to deliver enzyme replacement therapeutic drugs to cells of several organs of the body including the brain and central nervous system, eyes, ears, lungs, bone, heart, kidney, liver, and spleen for treating lysosomal diseases.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 151.19K | Year: 2010

DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I proposal develops a technology that allows bioactive proteins to be synthesized and secreted from cultured plant cells in high yields and with prolonged serum half-life. The innovation of this technology, designated Hyp-Glyco, involves the expression of secreted therapeutic proteins as fusions with a novel hydroxyproline (Hyp)-Glyco tag. The Hyp-Glyco tag also extends serum half-life and facilitates purification of secreted proteins while retaining protein bioactivity. This proposal is focused on scale-up process development of Hyp-Glyco technology in bioreactor cultured tobacco cells expressing interferon 2b and in development of a cost-effective technique for protein recovery/purification. Specific aims of this feasibility Phase I are to 1) Establish bioreactor based high yield interferon protein production in plant cell cultures using Hyp-Glyco technology; 2) Demonstrate that continuous perfusion culture technology will further enhance protein production; and 3) Show that reliable and cost-effective recovery and purification of bioactive interferon protein can be achieved in bioreactor grown plant cell cultures. Success of Phase I will support a follow-up Phase II aimed at establishing cost-effective commercial level production protocols for all phases of this new protein production technology so as to provide the confidence necessary for investing in Phase III commercial development. Protein therapeutics represents a multi-billion-dollar marketplace, but costly manufacturing methods for these drugs currently make them prohibitive for consumers. The broad impact of the proposed work resides in the potential of an alternative less costly platform for enhanced production of therapeutic proteins in plant cells which would, simultaneously, provide the added advantage of improved clinic effectiveness. Because this technology not only produces high-yield secreted proteins but also eliminates the time-consuming and expensive process of chemical derivatization to improve clinic effectiveness, the production costs can be significantly reduced. With the additional safety advantage of substituting plant cells for existing animal cell production, molecular farming could become commercially competitive with current mammalian and microbial cell production systems. Importantly, the interferon with extended serum half-life described here would meet a significant demand from 4 million hepatitis C virus (HCV) infected patients in USA and 3% of population worldwide. This technology is also broadly applicable to a wider range of therapeutically important proteins such as hGH, G-CSF and EPO etc, all of which represent billion-dollar markets. The development and success in commercializing the Hyp-Glyco protein manufacturing technology would create job opportunities in economically disadvantaged regions of the US and drive local economic development. PUBLIC HEALTH RELEVANCE: The growing dual threat of environmental pollution and global warming is considered by most health/medical experts and governments as one of the most dangerous and intransigent potential health problems globally. The need for developing new health positive, cost conscious and environmentally sustainable technologies for production of industrial and pharmaceutical products is a high priority of health related research in the U.S. and abroad. This proposal will target this need directly by developing and testing the feasibility of innovative more cost-effective methods for producing therapeutic proteins by using plant-based cultures and bioreactors which will confer the simultaneously benefits of greater safety, energy conservative and environmental sustainability than traditional manufacturing methods.

Discover hidden collaborations