DUBLIN, OH, United States
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Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 223.74K | Year: 2015

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Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 170.71K | Year: 2015

DESCRIPTION provided by applicant The RNA interference RNAi mediated gene silencing has become an important technology for manipulating cellular phenotypes mapping genetic pathways and discovering therapeutic targets and has therapeutic potential A key challenge to realizing the broad potential of RNAi technology is the need for safe and effective methods for delivery Small interfering RNA siRNA into targeted cell Although a variety of materials and approaches have been explored for siRNA delivery the performance of current materials and approaches remain unsatisfactory because they generally do not work well with primary cells or non adherent cell types and often result in some degree of cytotoxicity and alterations in cell biology thereby severely limiting the cell types amenable to discovery research and not suitable for human therapeutics In this project we propose to investigate a novel molecularly designed multi functional DNA Origami nanostructures DONs for effective delivery of siRNA inside targeted cells Our hypothesis is that the biocompatible molecularly defined monodispersed DONs incorporated with siRNAs and cell penetrating peptides CPP would enables effective siRNA uptake by cells and efficient release of siRNA inside cells resulting in high gene knockdown even when using low siRNA concentrations Our ultimate goal is to develop a safe and effective DONs siRNA therapeutic for diseases the short term goal of this Phase I project is to develop DONs based multi functional siRNA delivery and transfection reagent with optimal structure to aid siRNA silencing research The Phase I proof of concept demonstration project will focus on developing chemistry and protocol for constructing DONs siRNA and in vitro assessing the effectiveness of DONs siRNA for cell transfection and gene knockdown We plan to develop one pot approach to create multi functional DONs incorporated with firefly luciferase Luc siRNA gene and green fluorescent protein GFP siRNA gene and evaluate their silencing efficiency to Luc expressed HeLa cells and GFP expressed Human prostate carcinoma PC cells In Phase II we will thoroughly optimize the preparation of multi functional DON siRNA incorporated with cell target ligands investigate the in vivo delivery of DON siRNA and the effectiveness of gene knockdown the pharmacokinetic profile and organ biodistribution of DON siRNA in nude mice bearing tumors PUBLIC HEALTH RELEVANCE In this project we plan to use biological and biocompatible natural material the DNA as building blocks to create defined DNA nanostructures as delivery carriers for short interference RNA siRNA and test the effectiveness for gene knockdown in cells The successful completion of this project is expected to develop a new type of non immunogenetic and non cytotoxic cell transfection reagent which will have broad applications in biological biomedical and pharmaceutical research as well as potential for therapeutic drug development


The present invention is directed to an improved process for removing siloxanes from a biogas feed comprising (i) passing a gas feed through an adsorbent bed having an adsorbent having an inert surface to adsorb onto the adsorbent at least a portion of the siloxanes in the gas feed; and (ii) regenerating the adsorbent by removing siloxanes from the adsorbent. The adsorbent surface is rendered inert or nearly inert preferably via calcination.


Grant
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 99.69K | Year: 2015

Bacteriophages (phages), viruses which specifically infect and lyse bacteria, are attractive alternatives to antibiotic therapy as they are naturally occurring, amplify in the host, are inexpensive to produce and display narrow host ranges. This latter aspect is of particular interest to therapy as, unlike broad-spectrum antibiotics which kill the both the pathogen and endogenous bacterial flora, phages do not display off target effects. However, this selective host range typically necessitates that therapeutic phages must be developed for each bacterial pathogen, and that each preparation must contain a cocktail of phages to ensure adequate species coverage. The logistical requirements needed to develop phage cocktails are immense, often requiring the isolation, characterization and host range analysis of hundreds of phages. Therefore, the development of high-throughput technologies capable of mitigating these constraints is highly desirable. Our Phase I goal is to develop rapid high-throughput technologies for the development of phage cocktails. This will be accomplished by: 1) automated isolation of clonal phage by viral-tagging and fluorescence-assisted cell sorting, 2) preferential isolation of broad-host range lytic phages, and 3) high-throughput, microtiter plate based host range analyses based on luminescence.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.95K | Year: 2015

Collectively Phytophthora species are estimated to cost the agricultur industry tens of billions of dollars per year globally. Phytophthora capsici a fungus-like plant pathogen is a scurge of vegetable crops known to infect over 45 species including peppers, cucumbers, squash, cantaloupe, watermelon, zucchini, pumpkin, eggplant, tomatoes, snap beans and lima beans.Its complex life cycle high genetic variability, sexual reproduction, and ability survive in the soll for many years makes this pathogen a nightmare for farmers. Although similar in appearance to fungi, it is an oomycete and more closely related to certain algae than fungi. Because of this most agricultural chemicals used for treating plant pathogens being designed to kill fungi, are not as effective against oomycete pathogens like P. capsici. Under idea growth conditions no chemical treatment is effective against P. capsici. When this is combined with limited success in the development of vacines against P. capsici it is clear that new control strategies are desperately needed.Guild Associates proposes to conduct proof-of-concept study to develop an antisense based agent against P. capsici. Antisense agents work by blocking the production of a target protein rather than blocking its function as most chemical agents do. Using a military analogy most cheimical treatments work like tanks engaging enemy tanks on the battle field, whereas antisense agents work like a bomber destroying the factory that makes the tanks. Our firm is currently developing a similar antisense agent for use against the fungal human pathogen Aspergillus fumigatus using similar methods. We have already identified a type of transport peptide called a cell-penetrating peptide (CPP) that is effectively transported into the fungal pathogens A.fumigatus and Candida albicans. The first part of this study will evaluate other CPPs identified from the literature against our current top CPP for their ability to be transported into P. capsici. Then the top performing transporter will be further improved using rationally designed CPP libraries to evolve an improved product. Next we will use an antisense molecule (PMO) attached to this CPP to demonstrate we can use this agent to knockdown the production of a model fluorescent protein introduced into P. capsici. Finally we will develop and test a CPP-PMO that blocks the production of protein that is essential for growth of P. capsici producing an early-stage anti-P. capsici agent. Further refinement and optimization through a Phase II grant would allow this agent to be developed into an agent ready for field testingIt is believed that through the efforts of this project, a new treatment option for P. capsici infestations in the fields of vegetable crop farmers will be attained, not borrowed from other similar looking plant pathogens, but designed and taylored specifically to eliminate P. capsici from the farms of America. Because agents of this type are the progeny of the genomics era, they can be quickly designed using the genome of the targeted pest, and since they like DNA gain meaning by the order of their component parts (similar to how words attain meaning by the order of the letters) not by a unique complex chemical structure, different agents against the same organism will have similar chemical properties reducing the amount of testing necessary to bring them to market, producing new more effective drugs quicker. Thus this project will open the door to a new age of treatment options for farmers around the world that will reduce crop losses and improve the profitability of vegetable farming.


Grant
Agency: Department of Defense | Branch: Defense Health Program | Program: SBIR | Phase: Phase I | Award Amount: 149.91K | Year: 2014

Guild BioSciences proposes to develop a self-contained, low-cost, disposable, easy to use, colorimetric test strip that enables soldiers to measure/monitor salivary Adiponectin protein, a unique biomarker whose decreased circulating level is an indicator of weight-gain metabolic processes. The proposed test strip requires no special training to operate and results can be visibly read within ten minutes. To ensure the sensitive detection of the salivary Adiponectin at ng/mL level, innovative strip architecture and in-situ signal amplification will be integrated into the test strip. Specific efforts in Phase I will be directed to characterize the nature of adiponectin in human saliva by multiple biochemical methods. The performance of the prototype strip will be evaluated by measuring the Adiponectin level of human saliva samples from a human specimen repository. In Phase II, we will optimize and validate the test strip, investigate the correlation of Adiponectin level in saliva and blood, determine the cult-off value by analyzing a large number of clinical saliva samples, and refine manufacturing processes in preparation of mass production and commercialization.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2014

The long term goal of the project is to use malaria parasite specific low-molecular-weight metabolites as biomarkers for development of sensitive, low-cost, simple, battery-operated field-deployable urine or saliva diagnostic biosensor for detection of malaria infection. Four malaria parasite-specific metabolites (3-Methylindole, Succinylacetone, S-Methyl-L-thiocitrulline, O-Arachidonoyl Glycidol) recently identified by our metabolome analysis can potentially be used in the development of inexpensive and simple biosensor platforms for malaria diagnosis. This contract seeks to support CDC/MB studies by 1) generating biopolymer receptors against four malaria parasite-specific metabolites (3-Methylindole, Succinylacetone, S-Methyl-L-thiocitrulline, O-Arachidonoyl Glycidol) and 2) providing proof of concept in the use of inexpensive and simple biosensor platforms for detection of the target compounds. The detection of the above four malaria parasite-specific metabolites requires generation of biopolymer receptors, aptamers or antibodies, specific for the assay of these compounds. Once the receptors against the four compounds are ready, they should be respectively applied to various simple and inexpensive biosensors for detection of these compounds.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 170.09K | Year: 2014

DESCRIPTION (provided by applicant): Guild proposes to develop an antisense oligomer-based antifungal effective against the human pathogen Aspergillus fumigatus. With a 40%-60% mortality rate, invasive aspergillosis (IA) due to A. fumigatus now surpasses invasive candidiasis as the most frequent fungal cause of death, especially amongst immunocompromised patients. Successful therapy for IA with current antifungals is notoriously difficult due to poor clinical efficacy and the increasing emergence of drug resistant strains. Despite this acute need for novel therapeutic strategies, there has not been a new class of antifungals targeting A. fumigatus developed in over 12 years. Therefore, a novel approach is urgently needed to develop new anti-Aspergillus targeting strategies. Phosphorodiamidate morpholino oligomers (PMOs), synthetic uncharged analogs of nucleic acids, are an antisense biotechnology that functions by base pairing with target gene mRNA, producing steric blockade of the translational machiner


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 209.01K | Year: 2014

DESCRIPTION (provided by applicant): Biological RNAs undergo extensive post-transcriptional modifications. These modifications are important in promoting the accuracy and efficiency of gene expression in biological systems. To decipher the functions of RNA modifications, robust analytical tools and methods that enable scientists to monitor, manipulate, and transcriptome-wide mapping RNA modifications are highly needed. In this multi-phase SBIR program, Guild Biosciences Inc. (GBS) proposes to address thisissue by: 1) developing a library of affinity antibodies and peptide sequences specific to modified nucleosides by using phase-antibody display libraries and peptide phase-display library, 2) developing a novel immunoassay system- open immunocomplex assaywith the developed antibodies and peptides for rapid and quantitative detection of modified nucleotides in RNA samples, and 3) incorporating the immunoprecipitation capability of the developed affinity reagents with next-generation sequencing platform


Patent
Guild Associates | Date: 2015-03-25

The present disclosure relates to compositions, methods, systems and kits for the detection of microorganisms of the Shigella species, including S. flexneri, S. dysenteriae, S. sonnei, and S. boydii. The disclosure relates to recombinant phage operable to infect a S. flexneri microorganism, the phage comprising a detectable reporter. Detection systems of the disclosure may comprise a phage operable to infect a S. flexneri microorganism, and may comprise a reporter nucleic acid expressible upon infection of a S. flexneri microorganism by the phage. The system may be operable to detect the expression of the reporter. A detectable reporter may comprise any gene having bioluminescent, colorimetric and/or visual detectability. Live and infectious S. flexneri microbes may be detected by the compositions, methods, systems and kits described herein.

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