LINCOLN, NE, United States
LINCOLN, NE, United States

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Patent
Nature Technology Corporation | Date: 2016-12-12

The present invention relates to the production and use of covalently closed circular (ccc) recombinant plasmids, and more particularly to vector modifications that improve expression of said DNA molecules in the target organism.


Patent
Nature Technology Corporation | Date: 2016-09-30

The present invention relates to recombinant DNA molecules such as plasmids, non-viral vectors, viral vectors and hybrids thereof, and more particularly to vector modifications that improve expression of said DNA molecules in cell lines and organisms.


Williams J.A.,Nature Technology Corporation
Current Gene Therapy | Year: 2014

DNA vaccines are a rapidly deployed next generation vaccination platform for treatment of human and animal disease. DNA delivery devices, such as electroporation and needle free jet injectors, are used to increase gene transfer. This results in higher antigen expression which correlates with improved humoral and cellular immunity in humans and animals. This review highlights recent vector and transgene design innovations that improve DNA vaccine performance. These new vectors improve antigen expression, increase plasmid manufacturing yield and quality in bioreactors, and eliminate antibiotic selection and other potential safety issues. A flowchart for designing synthetic antigen transgenes, combining antigen targeting, codon-optimization and bioinformatics, is presented. Application of improved vectors, of antibiotic free plasmid production, and cost effective manufacturing technologies will be critical to ensure safety, efficacy, and economically viable manufacturing of DNA vaccines currently under development for infectious disease, cancer, autoimmunity, immunotolerance and allergy indications. © 2014 Bentham Science Publishers.


Patent
Nature Technology Corporation | Date: 2016-04-12

The present invention relates to the production and use of covalently closed circular (ccc) recombinant DNA molecules such as plasmids, cosmids, bacterial artificial chromosomes (BACs), bacteriophages, viral vectors and hybrids thereof, and more particularly to vector modifications that improve expression of said DNA molecules.


Patent
Nature Technology Corporation | Date: 2013-03-14

The present invention relates to the production and use of covalently closed circular (ccc) recombinant plasmids, and more particularly to vector modifications that improve expression of said DNA molecules in the target organism.


Patent
Nature Technology Corporation | Date: 2015-02-03

General methods and strains of bacteria are described that dramatically simplify and streamline plasmid DNA production. In one preferred embodiment, endolysin mediated plasmid extraction combined with flocculation mediated removal of cell debris and host nucleic acids achieves increased yield and purity with simplified downstream purification and reduced waste streams, thus reducing production costs.


Patent
Nature Technology Corporation | Date: 2015-02-03

General methods and strains of bacteria are described that dramatically simplify and streamline plasmid DNA production. In one preferred embodiment, endolysin mediated plasmid extraction combined with flocculation mediated removal of cell debris and host nucleic acids achieves increased yield and purity with simplified downstream purification and reduced waste streams, thus reducing production costs.


Patent
Nature Technology Corporation | Date: 2015-02-03

General methods and strains of bacteria are described that dramatically simplify and streamline plasmid DNA production. In one preferred embodiment, endolysin mediated plasmid extraction combined with flocculation mediated removal of cell debris and host nucleic acids achieves increased yield and purity with simplified downstream purification and reduced waste streams, thus reducing production costs.


Patent
Nature Technology Corporation | Date: 2013-11-18

The present invention relates to the production and use of covalently closed circular (ccc) recombinant DNA molecules such as plasmids, cosmids, bacterial artificial chromosomes (BACs), bacteriophages, viral vectors and hybrids thereof, and more particularly to vector modifications that improve expression of said DNA molecules.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 247.93K | Year: 2013

DESCRIPTION (provided by applicant): To commercialize non-viral gene medicines, it is critical that both vector potency (i.e. therapeutic transgene expression levels) and the duration of the therapeutic effect be improved. Potent dose-sparing extended duration gene therapies will have a cost and efficacy competitive advantage over alternative technologies. In this Phase I proof of concept study, we will create a novel antibiotic-free MiniPlasmid gene therapy platform for extended duration gene therapy. Thevectors combine transient expression enhancers that improve transgene expression levels with a novel 270 base pair replication origin-antibiotic free selection cassette that we hypothesize will promote long duration gene expression after vector delivery tothe body. The MiniPlasmid platform will be applied to create a wound healing gene therapy product to treat diabetic neuropathic foot ulcers. In Specific Aims 1 and 2 a high yielding MiniPlasmid fermentation manufacturing platform is created. In SpecificAim 3 the MiniPlasmid vector platform is validated in vivo for extended duration expression compared to conventional plasmids. A hypoxia- inducible factor 1 (HIF-1 ) based gene medicine for diabetic foot ulcer treatment is developed utilizing an extendedhalf-life oxygen resistant highly active HIF-1 mutant (CA5-HIF-1 ). Specific Aim 3 is performed in collaboration with wound healing gene therapy expert Dr. John Harmon at Johns Hopkins University. The MiniPlasmid vector platform is designed to improvetransgene expression levels and duration to enable gene medicine development for multiple applications requiring extended duration expression. MiniPlasmid vectors developed in Phase I will be marketed to investigators for a variety of gene therapy applications through publications, trade shows, and the Nature Technology Corporation (NTC) website. In Phase II the HIF-1 MiniPlasmid gene therapeutic will undergo preclinical safety and efficacy evaluations for treatment of diabetic foot ulcers prior to clinical development in Phase III. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The objective of this proposal is to develop a novel antibiotic-free non-viral MiniPlasmid gene therapy platform for extended duration gene therapy, and as such is responsive to NIGMS SBIR high-priority area of interest in development of improved vectors for gene transfer. The vectors combine transient expression enhancers that improve transgene expression levels with a novel replication origin-antibiotic free selectioncassette that affords long duration gene expression after gene delivery to the body. The platform will be applied to create a wound healing gene therapy product to treat diabetic neuropathic foot ulcers.

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