ATP Project Brief2004 General Competition (September 2004)A Genetic Engineering Technology Platform for Production of Novel Cyclic Peptide-Based DrugsDiagnostic and Therapeutic Biotechnology |
Develop methodologies and tools to enable simple, efficient genetic engineering of biosynthesis complexes to produce cyclic peptides for use as antifungal, antibacterial and anticancer drugs. Sponsor: AureoGen Biosciences, Inc.SMIC, suite 12004717 Campus Drive Kalamazoo, MI 49008 |
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There is an immediate need for novel drugs for the treatment of fungal infections, (antibiotics resistant) bacterial infections, and cancer. Cyclic peptides constitute a class of compounds that have made crucial contributions to the treatment of these diseases. Penicillin, Vancomycin, Cyclosporin, the Echinocandins and Bleomycin are well-known cyclic peptides. Although cyclic peptides can be very efficient drugs, they are complex natural products, produced by microorganisms such as bacteria and fungi. These organisms contain large enzyme complexes called "non-ribosomal peptide synthetase" (NRPS) complexes that constitute a microscopic assembly line for producing cyclic peptides. The structure of a cyclic peptide is narrowly defined by the organism that produces it, and because of their complexity, it is difficult and expensive to make even minor modifications synthetically. Current compounds are either native or native with minor modifications. Hence, the full potential of cyclic peptides for the treatment of human diseases has not been explored. In addition, there are cyclic peptide-based drugs with excellent clinical properties that cannot be commercialized because the required modifications cannot be made economically by synthetic chemistry. AureoGen Biosciences proposes to develop methodologies and a set of genetic tools that will allow simple, efficient engineering of tailored NRPS complexes to synthesize specific cyclic peptides in the producer organisms. If successful, this NRPS engineering platform will enable not only simple modifications to existing cyclic peptides, but also the design and synthesis of entirely novel cyclic peptides, creating the means for cost-effective production of both improved versions of existing antibacterial, antifungal and cancer drugs, as well as entirely novel compounds for the treatment of these diseases. The market for drugs in these three disease areas presently exceeds $40 billion and is growing rapidly. In addition to generating novel drugs, the successful construction of the described cyclic peptide genetic engineering platform has the potential to create a new biotechnology industry with a scope far beyond that of the pharmaceutical industry. Additional applications include the production of vaccines, base chemical reagents, toxins, and cosmetics. AureoGen Biosciences is a small company with limited resources. Without ATP funding this project would not be pursued due to the significant challenges associated with the engineering of NRPS gene sequences from different organisms. ATP funding will result in a savings of six to eight years in the implantation of this technology, and thus expedite the introduction of novel life-saving drugs on the market. |
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This is the fact sheet for this project as it was announced on September 28, 2004. Date created: 9/28/2004 |