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Auctus Biologics, Inc., under the leadership of Ichor Life Sciences, demonstrated the feasibility of a novel optical biosensor chip technology designed to facilitate the screening, validation, and development of novel drugs and their biological targets using a biophysical technique known as Surface Plasmon Resonance (SPR). SPR is the gold standard for studying biomolecular interactions in the pharmaceutical and biotechnology industries and is indispensable in characterizing the interactions between small molecule drugs and their protein targets involved in myriad diseases. Over the course of the grant, Auctus scientists worked to create a prototype of the technology, named RPtag Capture, and investigated its generalizability, robustness, and versatility, culminating in a battery of experiments to validate data produced with this system against current state-of-the-art SPR chip capture chemistries and benchmark biomolecular interactions. Though the RPtag Capture technology was found to have numerous useful laboratory and research applications that Auctus continues to investigate and develop, the platform did not exhibit sufficient generalizability to enable commercialization. From a pedagogical perspective, this grant provided the opportunity to train numerous technicians, graduate students, and postdoctoral fellows in both recombinant protein production and SPR-based biophysical techniques, which was an unparalleled training and professional development experience normally available only to experts in the field.
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\nModified by: Brandon S Moyer
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![\"Schematic](\"/por/images/Reports/POR/2024/2129469/2129469_10784477_1707263931540_RPtag_Capture--rgov-66x44.jpg\")
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Immobilized RPlarge binds RPsmall-fusion targets with low pM affinity, leading to capture dissociation half-life of multiple hours. In this highly versatile system, the ligand / analyte roles of RPlarge and RPsmall can be reversed.
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Brandon S. Moyer
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Schematic of the RPtag Capture system
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\n","publicAccessMandate":"1","startDate":"02/15/2022","title":"SBIR Phase I: Development of an Optical Biosensor to Facilitate Screening, Validation, and Development of Novel Drugs and their Biological Targets","transType":"Standard Grant","ueiNumber":"CU1LAPDBMJD1"},{"abstractText":"The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to improve the health and quality of life for the 15-30 million Americans suffering from celiac disease (CD) and other gluten-related disorders, especially those with poor management of symptoms. Gluten-related disorders have a combined global prevalence of 5–10% and have been increasing over the past decade. Currently, the only effective treatment for these patients is adherence to a strict gluten-free diet, which fails to relieve symptoms in all patients and cannot prevent the severe gastrointestinal distress that follows accidental exposure. This project will advance a therapeutic solution to prevent persistent symptoms related to low-level or accidental gluten exposure. This will provide protection for people with CD and non-celiac gluten sensitivity when traveling, new patients adapting to a gluten-free diet, and individuals whose symptoms are poorly controlled despite adherence to a gluten-free diet. \r\n\r\nThe proposed project will leverage a novel bacteriophage-based microbiome engineering platform to advance the development of a product to provide protection from gastrointestinal distress stemming from gluten exposure. To develop this therapeutic phage product, phages capable of infecting common gut bacteria like E. coli will be identified and engineered for efficient lysogenization. The phage or phage cocktail will be further engineered to express therapeutic modalities/proteins and tested in both human organoids derived from patients with CD and mouse models to demonstrate efficacy. The proposed work will provide a foundation for future extension of the platform to a wide range of microbiome-based applications.\r\n\r\nThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"VULCAN BIOLOGICS INC","awardeeAddress":"27 ANGELOU ST","awardeeCity":"IRVINE","awardeeCountryCode":"US","awardeeDistrict":"47","awardeeDistrictCode":"CA47","awardeeName":"Vulcan Biologics, Inc.","awardeePhone":"8577539032","awardeeStateCode":"CA","awardeeZipCode":"926174064","cfdaNumber":"47.041, 47.084","date":"12/08/2021","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"989854","expDate":"11/30/2023","fundAgencyCode":"4900","fundProgramName":"SBIR Phase II","fundsObligated":["FY 2022 = $989,854.00"],"fundsObligatedAmt":"989854","histAwd":"false","id":"2126838","initAmendmentDate":"12/08/2021","latestAmendmentDate":"12/08/2021","managingPec":"537300","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Michael Koeris","perfAddress":"","perfCity":"","perfCountryCode":"US","perfDistrict":"47","perfDistrictCode":"CA47","perfLocation":"MARCADOR CORP.","perfStateCode":"CA","perfZipCode":"926174064","pi":["Michael Koeris mike@aresinnovation.com"],"piEmail":"mike@aresinnovation.com","piFirstName":"Michael","piId":"270037775","piLastName":"Koeris","poEmail":"epiersto@nsf.gov","poName":"Erik Pierstorff","poPhone":"7032920000","primaryProgram":["01002223DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537300","program":"BIOLOGICAL CHEMISTRY","progRefCode":"1982","publicAccessMandate":"1","startDate":"12/15/2021","title":"SBIR Phase II: Bacteriophage-Based Microbial Gene Therapy Platform for In Situ Engineering of Microbiomes","transType":"Cooperative Agreement","ueiNumber":"LNBVDMU2KNN5"},{"abstractText":"The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to develop the first small RNA-based vaccination approach for mature trees, vines, and bushes against Xylella fastidiosa (XF), one of agriculture’s most devastating bacterial diseases. XF diseases include (1) Olive Quick Decline Syndrome, which is currently threatening the entire Southern Europe olive industry and killing trees that are over 1,000 years old; (2) Pierce’s Disease, which has severely damaged Southern California vineyards; and (3) Citrus Variegated Chlorosis, which is one of several diseases threatening the citrus industry. This project is based on a novel infectious RNA discovered by the Company’s team that can be used as a delivery vehicle for anti-pathogenic agents to target XF. A single inoculation can potentially provide lifetime protection while not harming the tree. As of today, there is no vaccination or cure for XF. If successful, this would represent a new platform potentially capable of vaccinating most trees against most fungal, bacterial, and viral diseases. In the absence of treatment, in a few decades, citrus, olives, and many other valuable crops that produce food for millions of people may cease to exist outside of insect-protective structures like greenhouses. \r\n\r\nThe proposed project has four key milestones required to defeat XF: (1) identify small interfering RNAs (siRNAs) capable of targeting gene expression in a Gram-negative bacterium like XF, which has never been accomplished commercially, and integrate these siRNAs into a novel delivery vector, which can systemically infect plants with no apparent host range; (2) demonstrate that sufficient siRNAs are generated in phloem companion cells in a laboratory host to reduce titers of XF in the xylem where it exclusively resides; (3) show that the Company’s novel RNA vector, which can systemically infect all commercial varieties of citrus, can also systemically infect olive trees and/or grapevines; (4) amplify the RNA vector in trees susceptible to XF and demonstrate efficacy against XF in greenhouse trials. The proposed work will address the first two objectives in the model plant N. bethamiana and the third objective in olive and grapevines.\r\n\r\nThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"SILVEC BIOLOGICS, INC","awardeeAddress":"200 GIRARD ST STE 200","awardeeCity":"GAITHERSBURG","awardeeCountryCode":"US","awardeeDistrict":"06","awardeeDistrictCode":"MD06","awardeeName":"SILVEC BIOLOGICS, INC.","awardeePhone":"3104636625","awardeeStateCode":"MD","awardeeZipCode":"208773490","cfdaNumber":"47.084","date":"02/05/2021","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"255990","expDate":"01/31/2022","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 2021 = $255,990.00"],"fundsObligatedAmt":"255990","histAwd":"false","id":"2035639","initAmendmentDate":"02/05/2021","latestAmendmentDate":"02/05/2021","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Feng Gao","perfAddress":"9600 Gudelsky Dr","perfCity":"Rockville","perfCountryCode":"US","perfDistrict":"08","perfDistrictCode":"MD08","perfLocation":"Silvec Biologics Inc.","perfStateCode":"MD","perfZipCode":"208503467","pi":["Feng Gao fgao@silvec.com","FENG GAO (Former) feng_gao@subr.edu"],"piEmail":"fgao@silvec.com","piFirstName":"Feng","piId":"270036912","piLastName":"Gao","poEmail":"epiersto@nsf.gov","poName":"Erik Pierstorff","poPhone":"7032920000","primaryProgram":["01002122DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537100","program":"AGRICULTURAL BIOTECHNOLOGY","progRefCode":"9109","projectOutComesReport":"
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Fruit trees such as grapevines and citrus represent around 20% of global agriculture production value. One of the most dangerous plant bacterial pathogens worldwide, Xylella fastidiosa (Xf), capable of infecting economically important trees like olives (Olive Quick Decline Syndrome) and grapevine (Pierce's Disease), is currently spreading at alarming rates. There is a lack of biological control strategies available to protect trees and vines against Xf and many other microbial pathogens. In this context, Silvec Biologics has developed an RNA-based technology that can be used to defeat microbial pathogens currently threatening the fruit tree industry in the USA and worldwide. This method works by delivering RNA molecules inside trees designed to target invasive pathogens for degradation and to aid the plant's immune system.
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Silvec has spent several years optimizing methods to ensure an efficient and economically viable means of delivering small anti-pathogenic RNA molecules into trees to protect against Xf as well as several viral and fungal pathogens. It has focused to date on model plant systems and is now scaling up to demonstrate it technology by silencing a pathogen in its natural host tree.
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In this NSF-SBIR project, Silvec's goal is to defeat Xf, as well as potentially other microbial pathogens, in trees starting with grapevines. Silvec had identified 3 milestones in its phase I project that needed to be overcome to defeat Xf: (1) develop an siRNA able to target gene expression in a gram negative bacterium like Xf; (2) demonstrate that sufficient siRNAs are generated in phloem companion cells by its vector to reach the xylem where Xf resides; and (3) show that its vector can systemically infect trees and/or grapevines. This was to then be followed by a Phase II project to optimize the process and scale up to immunizing grapevines against Xf and demonstrating efficacy in growth rooms / greenhouse trials.
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In phase I conducted between Feb 2021 to Jan 2022, Silvec has 1) developed multiple small RNAs (siRNAs) targeting Xf and have demonstrated the ability to substantially silence Xf colonizing the xylem of model plant N. benthamiana. It has also demonstrated an inoculation process to introduce the vector into grapevines and have detected it in systemic tissue and new leaves (including minus strands), indicating that the vector is moving systemically and replicating.
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These highly encouraging results position us well for Phase II of this project where Silvec expects to not only be able to target a bacterial target like Xf, but also to immunize grapevines against other economically important microbial targets including viruses and fungi using its vector.
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\n\t\t\t\t \tLast Modified: 03/30/2022
\n\t\t\t\t\tModified by: Feng Gao
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","publicAccessMandate":"1","startDate":"02/15/2021","title":"SBIR Phase I: Using a novel RNA therapy to immunize trees and vines against deadly bacteria","transType":"Standard Grant","ueiNumber":"ZH7KBVHXP1C3"},{"abstractText":"The broader impact of this Small Business Innovation Research (SBIR) Phase I project will be the stable and persistent modulation of microbiomes – the community of microorganisms that populate the different regions of a person’s body. All organisms have an associated microbiota that play an intimate role in that organism’s growth, health, immunity, and stress tolerance. Current approaches for modulating the microbiome, including the use of prebiotics, probiotics, and other living therapeutics, lack a demonstrated ability to induce long-term changes in the microbiota. In contrast, this project uses bacteriophages—viruses that infect bacteria but do not affect the human host—for long-term or permanent alteration of resident bacterial members of the microbiome. As a proof of concept, initial development will focus on altering human gut microbes to treat gluten-related disorders, ranging from mild gluten sensitivity to celiac disease. Ultimately, this technology could be adapted to address a vast number of microbiome-related issues that span a wide range of clinical, commercial, and societal interests. Potential health applications include microbiome-related conditions such as obesity, type 2 diabetes, atherosclerosis, cardiovascular disease, inflammatory bowel disease, autoimmune disorders, gingivitis and caries, multiple types of cancer, skin disorders, and recurrent bacterial infections. Other potential applications include agricultural and environmental fields.\r\n\r\nThe proposed project will exploit the utility and power of bacteriophages to transduce genetic information. As engineering bacteriophages to modulate the microbiome has not yet been attempted beyond preliminary proof-of-concept experiments, establishment of the proposed microbial gene therapy platform will require research and development efforts to overcome numerous technical challenges. The objectives of this project include: 1) engineering Bifidobacterium-targeting temperate bacteriophage capable of infecting B. longum to express a gluten-degrading enzyme from Sphingomonas capsulata and 2) introducing the glutenase-expressing phage into a B. longum in vitro biofilm model. This project will result in enhanced knowledge of bacteriophage–host interactions, genetic circuit modulation, and management of horizontal gene transfer, which will have far-reaching implications for innovation in the fields of applied virology, genetic engineering, and microbiomics. In particular, the ultimate success of this project will rely upon the use and development of synthetic biological approaches to enhance bacteriophage capabilities, such as flexibly integrating and excising genes from host genomes, managing intra-host expression, converting phages between lifestyles (e.g. lytic to lysogenic and back), expanding phage host range, and neutralizing bacterial host defense systems.\r\n\r\nThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"VULCAN BIOLOGICS INC","awardeeAddress":"27 ANGELOU ST","awardeeCity":"IRVINE","awardeeCountryCode":"US","awardeeDistrict":"47","awardeeDistrictCode":"CA47","awardeeName":"Vulcan Biologics, Inc.","awardeePhone":"8577539032","awardeeStateCode":"CA","awardeeZipCode":"926174064","cfdaNumber":"47.084","date":"05/15/2020","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"225000","expDate":"03/31/2021","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I, SBIR Outreach & Tech. Assist","fundsObligated":["FY 2020 = $225,000.00","FY 2021 = $20,000.00"],"fundsObligatedAmt":"245000","histAwd":"false","id":"2014888","initAmendmentDate":"05/15/2020","latestAmendmentDate":"01/22/2021","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Michael Koeris","perfAddress":"27 Angelou Street","perfCity":"Irvine","perfCountryCode":"US","perfDistrict":"47","perfDistrictCode":"CA47","perfLocation":"MARCADOR CORP.","perfStateCode":"CA","perfZipCode":"926174064","pi":["Michael Koeris mike@aresinnovation.com"],"piEmail":"mike@aresinnovation.com","piFirstName":"Michael","piId":"270037775","piLastName":"Koeris","poEmail":"epiersto@nsf.gov","poName":"Erik Pierstorff","poPhone":"7032920000","primaryProgram":["01002122DB NSF RESEARCH & RELATED ACTIVIT","01002021DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537100, 809100","program":"Synthetic biology, Biotechnology","progRefCode":"144E, 8038","projectOutComesReport":"
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In this Phase I project Marcador Corp, now Vulcan Biologics, initiated development of a platform of synthetic biology technologies to efficiently and stably engineer bacteria present within a human microbiome using temperate (non-virulent) bacteriophage that would allow for therapeutic treatment of a variety of illnesses or diseases. These phages are viruses that infect specific bacteria and then alter their DNA in order to have them to produce potentially therapeutic compounds, but are unable to infect human cells. During the period of this work, we have developed a highly efficient method to insert genes of interest in a site-specific manner into the genome of the phage. Furthermore, we have demonstrated the ability of these engineered phage to infect target bacteria, integrate into the bacterial chromosome and express the introduced genes. To this end we have successfully engineered phage to express 3 different reporter genes as a means to rapidly evaluate the potential of the technology. Additionally, we have evaluated three different promoters to demonstrate the ability to regulate levels of gene expression.
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In addition to the development of a robust phage engineering technology, another objective of this Phase I project was to demonstrate expression of a glutan degrading enzyme for use in the alleviation of symptoms associated with celiac disease and gluten sensitivity. We successfully engineered both an anaerobic and facultative anaerobic bacterium to produce multiple gluten degrading enzymes. To enhance secretion of the various enzymes we also evaluated a series of signal peptides and carrier fusion proteins in order to maximize available enzyme for the degradation of gluten.
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With the completion of this Phase 1 project we have established a robust phage engineering technology and demonstrated expression of a gluten degrading enzyme. This work puts us in position to develop a Phase 2 proposal that will lead to the development of a commercial solution to combat the debilitating effects of celiac disease and non-celiac gluten sensitivity.
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\n\t\t\t\t \tLast Modified: 02/10/2021
\n\t\t\t\t\tModified by: Michael Koeris
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","publicAccessMandate":"1","startDate":"05/15/2020","title":"SBIR Phase I: Bacteriophage-Based Microbial Gene Therapy Platform for In Situ Engineering of Microbiomes","transType":"Standard Grant","ueiNumber":"LNBVDMU2KNN5"},{"abstractText":"This NSF SBIR Phase I project takes a unique holistic approach to both tumor imaging and cancer drug delivery. This approach harnesses cancer cell proteins already in the body to allow selective delivery of tumor imaging agents or cancer-killing drugs to, and into, cancer cells. By choosing cancer-specific targeting proteins, the drugs will be transported primarily into cancer cells and undesirable off-target enrichment will be diminished. The goal is to mitigate drug uptake in non-cancerous fast-growing cells like; heart cells, bone marrow, skin or hair follicles. Treated patients will benefit from improved effectiveness of their cancer therapies. Such selective delivery should permit lower dosages of drug to be administered while also lowering the risks of unwanted, problematic side-effects. This cost-effective approach is well supported by the NSF?s core mission for the technical development of innovative drug delivery systems. \r\n\r\nIt remains challenging to provide sensitive tumor diagnosis and near-simultaneous assessments of response to cancer treatments in treated individuals. Of all the standard monitoring modalities, radiographic examination has been the most widely used to measure treatment response. However, some studies suggest up to 10-40% of cancers may not be measurable by currently available technologies. Various delivery approaches have been used to take advantage of endogenous molecules to transport imaging agents or drugs with increased specificity into cancer cells. Most of these approaches utilize macromolecular ligands or cell surface receptor binding approaches. This proposal takes a mechanistically innovative small-molecule approach. By harnessing the activities of endogenous inflammatory proteins produced in abundance by cancer cells and by cells within the tumor micro-environment, small molecule cancer drugs can be transported with efficiency to the site of their intended effect. Selective and accurate placement of a chemically-related diagnostic agent into cancer cells should allow a cost-effective, more personalized and exceedingly sensitive view of treatment response.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"","awardeeAddress":"819 North 49th Street, STE 307","awardeeCity":"Seattle","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"WA07","awardeeName":"RJS Biologics L.L.C.","awardeePhone":"2065175068","awardeeStateCode":"WA","awardeeZipCode":"981036577","cfdaNumber":"47.084","date":"06/28/2017","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"225000","expDate":"04/30/2019","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 2017 = $225,000.00"],"fundsObligatedAmt":"225000","histAwd":"false","id":"1720789","initAmendmentDate":"06/28/2017","latestAmendmentDate":"02/04/2019","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Stephen M McCraith","perfAddress":"Suite 307, 819 N. 49th St.","perfCity":"Seattle","perfCountryCode":"US","perfDistrict":"07","perfDistrictCode":"WA07","perfLocation":"RJSBio, Inc.","perfStateCode":"WA","perfZipCode":"981036577","pi":["Stephen M McCraith s_mccraith@yahoo.com"],"piEmail":"s_mccraith@yahoo.com","piFirstName":"Stephen","piId":"269837706","piLastName":"McCraith","piMiddeInitial":"M","poEmail":"hahn@nsf.gov","poName":"Henry Ahn","poPhone":"7032927069","primaryProgram":["01001718DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537100","program":"SMALL BUSINESS PHASE I, Biotechnology","progRefCode":"5371, 8038","projectOutComesReport":"
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Despite great progress in cancer therapeutics over the last decade, current cancer drugs may still cause harm and great distress to significant percentages of treated individuals. People treated for cancer should not lose their hair when there are no cancerous cells in their hair follicles. Children treated for cancer should not suffer lasting heart damage when there are no cancerous cells in their hearts. Individuals undergoing cancer treatment should not suffer from painful and disfiguring whole-body rashes, peripheral nerve damage, nor GI problems. We need cancer therapies that target cancer cells with more precision so healthy cells remain healthy during an individual?s cancer treatment. Ideally, cancer therapies would not cause harm to healthy cells.
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With the assistance of our NSF Phase I SBIR grant, RJSBIO, Inc. (Seattle, WA) is creating a new way of directing chemotherapeutics to cancer cells while decreasing the unwanted side effects on normal cells.
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At RJSBIO we make cancer drugs that are more capable of specifically delivering themselves to, and into, cancer cells. We have focused our NSF funded research efforts on engraving a tumor delivery functional element within small molecules as a requisite component of future cancer drugs and tumor diagnostic agents. Adding these elements to cancer drugs results in more precise and specific delivery into cancer cells.
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With our current NSF funding, we have created fully synthetic, non-peptide, small-molecule tumor imaging agents. These small molecules incorporate our delivery elements and radioactive tracers which allow us to track compound localization within tumor bearing mice. We have demonstrated a 1.7 fold enrichment of our addressed molecule in tumors representing lung cancers vs the parental non-addressed molecule (Fig. 1). More cancer drug on point within a tumor means less drug in the wrong place. Giving cancer drugs instructions on where they need to go is a good thing.
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Broader Impacts:
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1) The primary impact of our proposal is to provide a cost-effective, broadly applicable platform technology for the rapid development of improved cancer diagnostic agents and more precise cancer drugs.
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2) RJSBio?s fully-synthetic, small-molecule, approach represents a paradigm shift by targeting cancer promoting pathways and manipulating these paths like Trojan horses to instead deliver tumor imaging agents and cancer drugs.
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3) By pairing companion imaging agents with RJSBIO?s delivered cancer drugs, it will be possible to provide a more accurate picture of a cancer patient?s disease status, treatment options, and prognosis.
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4) The long-term impact of this technology is expected to extend well beyond the bounds of cancer and will likely reach across into other indications, in particular inflammation.
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5) More accurate cancer drugs should be more predictable in the clinic. This predictably should dramatically reduce the costs of bringing new cancer drugs to the market.
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We are most grateful to the NSF for their assistance.
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RJBIOs-DOTA-conjugate distribution in mice inoculated with human lung carcinoma cells.A.Representative tumor in mouse shoulderB.PET imaging of RJSBIOs delivered 68GA-DOTA C.A comparison of recovered radioactivity, delivered -vs- non-delivered, from mouse tumors at 300 minutes
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RJSBIO, Many thanks to P.S. U of MI
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Royalty-free (unrestricted use)
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Stephen M Mccraith
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Biodistribution studies of RJSBIOs-delivered DOTA
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","publicAccessMandate":"1","startDate":"07/01/2017","title":"SBIR Phase I: Rationally-designed, modular imaging agents for the targeted detection of tumors.","transType":"Standard Grant","ueiNumber":"EMN6JXXSEV31"},{"abstractText":"The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to develop natural alternatives to synthetic chemicals that are used to impart color to food, medicine, and cosmetics. Negative health impacts of some high volume synthetic colorants are driving demand for natural and safe colorants that are obtained from biological sources. This project will advance the commercial feasibility of a class of naturally occurring pigments that have properties of color, functionality, stability, and safety that make them attractive as food colorants. Based on six years of prior university research, a potentially suitable botanical source of a red pigment has been identified. The goal of this project is to develop a commercial process to produce the pigment from this botanical source. The pigment will be tested as a replacement for a synthetic red pigment that has been widely used as a food additive. The goal is to provide a natural alternative to reduce the health risks associated with artificial colorants.\r\n\r\nThis SBIR Phase II project proposes to develop a naturally occurring red pigment from a plant source as an alternative food color additive. Phase I demonstrated that the red pigment could be extracted at small-scale and performed well in food applications. The goal of this Phase II project is to scale up commercial processes for extraction and purification of this red pigment, and to conduct further performance testing. The pigment, which previously has not been available in commercial quantities, will be produced from a selected variety of a major crop species. The goal is to develop processes to scale pigment production under conditions that will validate a commercial scale. This will include the integration of mechanical separation, food grade extraction, and various commercially-available clarification systems. The products will be tested for performance characteristics and consistency of quality during scale up by examining thermal, pH, and light stability in a range of probable food and other applications. In addition, yield produced will be evaluated to validate economic competitiveness.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"REDLEAF BIOLOGICS, INC.","awardeeAddress":"145 GRAHAM AVE","awardeeCity":"LEXINGTON","awardeeCountryCode":"US","awardeeDistrict":"06","awardeeDistrictCode":"KY06","awardeeName":"RedLeaf Biologics Inc.","awardeePhone":"2059104277","awardeeStateCode":"KY","awardeeZipCode":"405060001","cfdaNumber":"47.084","date":"04/06/2017","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"750000","expDate":"09/30/2023","fundAgencyCode":"4900","fundProgramName":"SBIR Phase II","fundsObligated":["FY 2017 = $750,000.00","FY 2018 = $10,000.00","FY 2019 = $149,999.00","FY 2020 = $442,499.00"],"fundsObligatedAmt":"1352498","histAwd":"false","id":"1659039","initAmendmentDate":"04/06/2017","latestAmendmentDate":"11/02/2022","managingPec":"537300","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Jordan Wood","perfAddress":"145 Graham AV","perfCity":"Lexington","perfCountryCode":"US","perfDistrict":"06","perfDistrictCode":"KY06","perfLocation":"RedLeaf Biologics Inc.","perfStateCode":"KY","perfZipCode":"405460091","pi":["Jordan Wood Jordan@redleafbiologics.com","Stephen Pietsch (Former) sjpietsch@redleafbiologics.com"],"piEmail":"Jordan@redleafbiologics.com","piFirstName":"Jordan","piId":"269959387","piLastName":"Wood","poEmail":"epiersto@nsf.gov","poName":"Erik Pierstorff","poPhone":"7032920000","primaryProgram":["01001718DB NSF RESEARCH & RELATED ACTIVIT","01001819DB NSF RESEARCH & RELATED ACTIVIT","01001920DB NSF RESEARCH & RELATED ACTIVIT","01002021DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537300","program":"SBIR Phase IIB, SBIR Tech Enhan Partner (TECP), SMALL BUSINESS PHASE II, Biotechnology, SBIR/STTR CAP, EXP PROG TO STIM COMP RES","progRefCode":"165E, 169E, 5373, 8038, 8240, 9150","publicAccessMandate":"1","startDate":"04/01/2017","title":"SBIR Phase II: Biomanufacturing Red Natural Food Dye","transType":"Standard Grant","ueiNumber":"R5K9BFKK1KK7"},{"abstractText":"The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of an alternative to synthetic chemicals that are used to impart color to food. The food industry has a long history of using synthetic pigments that impart color to foods. However, there have been concerns about negative health impacts of some high volume synthetic colorants, and the food industry is increasingly interested in identifying colorants that are obtained from biological sources. This project will explore the technical and commercial feasibility of a class of naturally occurring pigments that have properties of color, stability, and safety that make them attractive as food colorants but for which a suitable source is not currently available. Based on six years of prior research, a potentially suitable botanical source of a red pigment has been identified, and now propose to develop a commercial process to produce the pigment from the botanical source.\r\n\r\nThis SBIR Phase I project proposes to develop a proof-of-concept pilot-scale process for extracting and purifying a naturally occurring pigment from a source plant. The pigment, which has not previously been available in commercial quantities, will be produced from a selected variety of a major crop species. Using mechanical separations, food grade solvent extractions, and various commercially-available food-grade adsorbants the goal is to produce pigment under conditions that can be used for proof-of-concept testing in model food products. The pigment produced will be characterized by analytical chemistry methods as a prelude to seeking FDA approval to sell the pigment for food use. The extracted pigment will be tested for performance characteristics, and for thermal, pH, and light stability in a range of probable food applications.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"REDLEAF BIOLOGICS, INC.","awardeeAddress":"145 GRAHAM AVE","awardeeCity":"LEXINGTON","awardeeCountryCode":"US","awardeeDistrict":"06","awardeeDistrictCode":"KY06","awardeeName":"RedLeaf Biologics Inc.","awardeePhone":"2059104277","awardeeStateCode":"KY","awardeeZipCode":"405060001","cfdaNumber":"47.084","date":"12/02/2015","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"150000","expDate":"12/31/2016","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 2016 = $179,999.00"],"fundsObligatedAmt":"179999","histAwd":"false","id":"1547738","initAmendmentDate":"12/02/2015","latestAmendmentDate":"06/21/2016","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Stephen Pietsch","perfAddress":"","perfCity":"","perfCountryCode":"US","perfDistrict":"06","perfDistrictCode":"KY06","perfLocation":"RedLeaf Biologics Inc.","perfStateCode":"KY","perfZipCode":"403568729","pi":["Stephen Pietsch sjpietsch@redleafbiologics.com"],"piEmail":"sjpietsch@redleafbiologics.com","piFirstName":"Stephen","piId":"269959387","piLastName":"Pietsch","poEmail":"rshuman@nsf.gov","poName":"Ruth Shuman","poPhone":"7032922160","primaryProgram":["01001617DB NSF RESEARCH & RELATED ACTIVIT"],"progEleCode":"537100","program":"SBIR Phase IB, SMALL BUSINESS PHASE I, Biotechnology, EXP PROG TO STIM COMP RES","progRefCode":"163E, 5371, 8038, 9150","projectOutComesReport":"
\n
Outcomes of this Small Business Innovation Research (SBIR) Phase I proof of concept project were the development of a natural alternative to synthetic chemicals that are used to enrich and impart color to edible or cosmetic products. This project explored the technical and commercial feasibility of a class of naturally occurring pigments that have properties of color, stability, and safety that make them attractive as food colorants but for which a suitable source is not currently available. During SBIR Phase I work, a successful proof-of-concept pilot-scale process was developed for extracting and purifying a naturally occurring pigment from a proprietary variety of a source plant species. The costs of producing the pigment were also modeled in order to evaluate economic feasibility. The composition of the pigment preparations was characterized by a variety of analytical methods. The product was tested in various food applications, such as dairy, candy, bakery and beverages, for performance characteristics, and for thermal, pH, and light stability in a range of probable food applications and found to be satisfactory for further commercialization. It was also discovered that the product had healthful antioxidant properties in vitro. The pigment, which has not previously been available in commercial quantities, was produced from a selected variety of a major crop species.
\n
\n\t\t\t\t \tLast Modified: 01/04/2017
\n\t\t\t\t\tModified by: Stephen Pietsch
\n
\n
\n
","publicAccessMandate":"0","startDate":"01/01/2016","title":"SBIR Phase I: Biomanufacturing Red Natural Food Dye","transType":"Standard Grant","ueiNumber":"R5K9BFKK1KK7"},{"abstractText":"This Small Business Innovation Research (SBIR) Phase I project will demonstrate the feasibility of using \"directed evolution\" to create highly active, selective hydroxylation enzymes for use in combinatorial biocatalysis of potential drugs. Such protein catalysts will be capable of direct hydroxylation of non-activated carbon centers without oxidation of other sensitive functionality; a transformation that is virtually impossible using traditional chemistry. Using highly active bacterial enzymes as a starting point, random mutants will be generated and clones capable of targeted hydroxylations will be selected by using by using high-through-put screening methods. Existing bacterial P450 enzymes do not have the required selectivity. Mammalian P450 systems that work effectively in-vivo, are difficult to express and are slow in catalysis. The potential of this technology for combinatorial library creation will be demonstrated using drug scaffolds.\r\n\r\nThe commercial application of the proposed technology will initially be to provide research oxidation catalysts for the development of new drug candidates. New classes of oxygenated candidates for testing will be prepared. Subsequently, the catalysts may be used in the actual synthesis of the new drugs.\r\n","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"","awardeeAddress":"125 Sidney Street","awardeeCity":"Cambridge","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"MA07","awardeeName":"Altus Biologics Inc","awardeePhone":"6172992900","awardeeStateCode":"MA","awardeeZipCode":"021394807","cfdaNumber":"47.084","date":"06/01/2004","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"99789","expDate":"12/31/2004","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 2004 = $99,789.00"],"fundsObligatedAmt":"0","histAwd":"false","id":"0419374","initAmendmentDate":"06/01/2004","latestAmendmentDate":"09/02/2004","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"James J Lalonde","perfAddress":"125 Sidney Street","perfCity":"Cambridge","perfCountryCode":"US","perfDistrict":"07","perfDistrictCode":"MA07","perfLocation":"Altus Biologics Inc","perfStateCode":"MA","perfZipCode":"021394807","pi":["James J Lalonde Lalonde@altus.com"],"piEmail":"Lalonde@altus.com","piFirstName":"James","piId":"000262956","piLastName":"Lalonde","piMiddeInitial":"J","poEmail":"","poName":"Om P. Sahai","poPhone":"","primaryProgram":["app-0104"],"progEleCode":"537100","program":"BIOELECTRONICS AND BIONETWORKS, BIOTECHNOLOGY","progRefCode":"9107, BIOT","publicAccessMandate":"0","startDate":"07/01/2004","title":"SBIR Phase I: Highly Active and Selective Hydroxylation Catalysts for Combinatorial Biocatalysis","transType":"Standard Grant","ueiNumber":""},{"abstractText":"9860988\r\n This Small Business Innovation Research Phase I project is directed the use a combination of cross-linked enzyme crystal (CLEC(R)) technology and chemical modification to prepare a stable and active biocatalyst for antibiotic synthesis. Beta-lactam antibiotic manufacturing processes are comprised of multiple protection, deprotection and stoichiometric activation steps, generating 100 to 1000 fold more waste than product. Moreover, energy consumption is high since many of the steps must be performed at ultra-low temperatures. Altus Biologics is a world leader in biocatalysis; developing cross-linked enzyme crystal (CLEC(R)) technology for the stabilization of protein catalysts. Development of a form of Penicillin acylase that is active and stable in aqueous/organic solvent mixtures will allow the exploitation of the exquisite selectivity of this enzyme for catalyzing a one-step antibiotic coupling. Optimization of catalyst activity and stability in high concentrations of reactants and solvent mixtures will be performed through iterative chemical modification and cross-linking.\r\n Development of a stable and active biocatalyst will allow the economic manufacture of high-volume pharmaceuticals via an efficient and environ-mentally benign process.\r\n\r\n\r\n\r\n","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"","awardeeAddress":"125 Sidney Street","awardeeCity":"Cambridge","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"MA07","awardeeName":"Altus Biologics Inc","awardeePhone":"6172992900","awardeeStateCode":"MA","awardeeZipCode":"021394807","cfdaNumber":"47.084","date":"10/30/1998","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"100000","expDate":"06/30/1999","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 1999 = $100,000.00"],"fundsObligatedAmt":"100000","histAwd":"false","id":"9860988","initAmendmentDate":"10/30/1998","latestAmendmentDate":"10/30/1998","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"James J Lalonde","perfAddress":"125 Sidney Street","perfCity":"Cambridge","perfCountryCode":"US","perfDistrict":"07","perfDistrictCode":"MA07","perfLocation":"Altus Biologics Inc","perfStateCode":"MA","perfZipCode":"021394807","pi":["James J Lalonde Lalonde@altus.com"],"piEmail":"Lalonde@altus.com","piFirstName":"James","piId":"000262956","piLastName":"Lalonde","piMiddeInitial":"J","poEmail":"","poName":"Cynthia J. Ekstein","poPhone":"","primaryProgram":["app-0199"],"progEleCode":"537100","program":"SYNTHESIS, SMALL BUSINESS PHASE I, GENERAL FOUNDATIONS OF BIOTECHNOLOGY, BIOTECHNOLOGY","progRefCode":"1948, 5371, 9183, BIOT","publicAccessMandate":"0","startDate":"01/01/1999","title":"SBIR Phase I: Development of a Stable, Heterogeneous Biocatalyst for Antibiotic Synthesis","transType":"Standard Grant","ueiNumber":""},{"abstractText":"This project deals with the development of a new type of stationary phase for chromatography and simulating moving bed (SMB) technology based on cross-linked protein crystals. While existing stationary phases can separate a wide variety of compounds, including mixtures of racemates, there are several limitations such as low loading, eluent limitations, narrow operational conditions and high cost, that preclude wider applications of chromatography. It is believed that some of these limitations can be successfully addressed by using Cross-Linked Enzyme Crystals (CLECá) or more broadly Cross-Linked Protein Crystals (CLPC). We have already demonstrated that cross-linked protein crystals are very stable, have porous structure, and demonstrate great affinity and chiral selectivity. In addition, they are mechanically stable and can be produced in large quantities. These crystals may have excellent performance characteristics as a new porous material and provide unique opportunities in at least three main types of liquid chromatography: size exclusion, affinity and chiral chromatography. In the Phase I study, the feasibility of using the five existing CLEC catalysts of lipases from Candida rugosa and Pseudomonas cepacia, subtilisin, thermolysin and penicillin acylase and a new CLPC derived from serum albumins as stationary phases for liquid chromatography will be demonstrated. The portion of synthetic chiral pharmaceuticals introduced as single enantiomers represents about $15 billion in sales and is expected to reach $150 billion by the end of the century. Chiral stationary phases could play and important role in producing and analyzing many of the final chemicals or intermediate used as optically pure drugs. The high price of bulk CSP currently precludes the wide use of this technology in either preparative chromatography or simulating moving bed (SMB) technology. This situation may dramatically change with the introduction of CSP based on protein crystals.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"","awardeeAddress":"125 Sidney Street","awardeeCity":"Cambridge","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"MA07","awardeeName":"Altus Biologics Inc","awardeePhone":"6172992900","awardeeStateCode":"MA","awardeeZipCode":"021394807","cfdaNumber":"47.084","date":"11/26/1996","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"75000","expDate":"06/30/1997","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 1997 = $75,000.00"],"fundsObligatedAmt":"75000","histAwd":"false","id":"9660460","initAmendmentDate":"11/26/1996","latestAmendmentDate":"11/26/1996","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Alexey L Margolin","perfAddress":"125 Sidney Street","perfCity":"Cambridge","perfCountryCode":"US","perfDistrict":"07","perfDistrictCode":"MA07","perfLocation":"Altus Biologics Inc","perfStateCode":"MA","perfZipCode":"021394807","pi":["Alexey L Margolin Margolin@Altus.com"],"piEmail":"Margolin@Altus.com","piFirstName":"Alexey","piId":"000232868","piLastName":"Margolin","piMiddeInitial":"L","poEmail":"","poName":"Joseph Hennessey","poPhone":"","primaryProgram":["app-0197"],"progEleCode":"537100","program":"BIOPROCESSING/BIOMOLECULAR MATERIALS, BIOTECHNOLOGY","progRefCode":"9181, BIOT","publicAccessMandate":"0","startDate":"01/01/1997","title":"SBIR Phase I: Protein Crystals as Novel Materials for Chromatography","transType":"Standard Grant","ueiNumber":""},{"abstractText":"This Small Business Innovation Research Phase I project deals with the development of a new type of biocatalysts by crystallization of enzymes on solid supports. Enzyme-catalyzed processes offer significant advantages over traditional chemical methods in organic syntheses, including superior efficiency, stereoselectivity and specificity. Yet, despite this enormous potential of enzymatic catalysis only a tiny portion of enzymes is used in the synthesis of fine chemicals or pharmaceuticals on an industrial scale. There are three major problems that preclude wider acceptance of enzymes as practical catalysts: enzymes are not stable enough, enzymes are fairly expensive, and in some cases - and this is especially important for the chiral resolutions- enzymes stereoselectivity is not high enough. Altus Biologics, Inc. believes that all these problems can be successfully addressed by using Cross-Linked Enzyme Crystals (CLECs). So far CLECs (microcrystals of 1-100 (m) have demonstrated excellent performance characteristics in the synthesis of optically pure compounds on a lab scale. Further scale-up of chemical processes (1-1000 kg) will require larger catalyst particles ( 1mm) which will be mechanically stable in both stir-tank and column reactors. To solve these problems researchers propose to design new catalysts by crystallization of enzymes onto solid supports with the following chemical crosslinking of the crystals. CLECs deposited onto solid surfaces (CLEC-SS) will offer significant advantages in the large-scale chemical processing. In this Phase I study, candida rugosa lipase (CRL) will be crystallized on the surface of glass beads and the properties of the catalyst will be thoroughly investigated.","activeAwd":"false","agency":"NSF","awardAgencyCode":"4900","awardee":"","awardeeAddress":"125 Sidney Street","awardeeCity":"Cambridge","awardeeCountryCode":"US","awardeeDistrict":"07","awardeeDistrictCode":"MA07","awardeeName":"Altus Biologics Inc","awardeePhone":"6172992900","awardeeStateCode":"MA","awardeeZipCode":"021394807","cfdaNumber":"47.084","date":"01/30/1995","dirAbbr":"TIP","divAbbr":"TI","estimatedTotalAmt":"65000","expDate":"11/30/1995","fundAgencyCode":"4900","fundProgramName":"SBIR Phase I","fundsObligated":["FY 1995 = $65,000.00"],"fundsObligatedAmt":"65000","histAwd":"false","id":"9461019","initAmendmentDate":"01/30/1995","latestAmendmentDate":"01/30/1995","managingPec":"537100","orgCodeDir":"15000000","orgCodeDiv":"15030000","orgLongName":"Directorate for Technology, Innovation, and Partnerships","orgLongName2":"Translational Impacts","orgUrl":"https://beta.nsf.gov/tip/ti","parentUeiNumber":"","pdPIName":"Alexey L Margolin","perfAddress":"125 Sidney Street","perfCity":"Cambridge","perfCountryCode":"US","perfDistrict":"07","perfDistrictCode":"MA07","perfLocation":"Altus Biologics Inc","perfStateCode":"MA","perfZipCode":"021394807","pi":["Alexey L Margolin Margolin@Altus.com"],"piEmail":"Margolin@Altus.com","piFirstName":"Alexey","piId":"000232868","piLastName":"Margolin","piMiddeInitial":"L","poEmail":"","poName":"Darryl G. Gorman","poPhone":"","primaryProgram":["app-0195"],"progEleCode":"537100","program":"PROJECTS, MANUFACTURING BASE RESEARCH, MANUFACTURING","progRefCode":"1978, 9146, MANU","publicAccessMandate":"0","startDate":"02/01/1995","title":"Crosslinked Enzyme Crystals Deposited on Surfaces as a Novel Type of Catalyst for Large Scale Chemical Processing","transType":"Standard Grant","ueiNumber":""}],"metadata":{"offset":0,"rpp":25,"totalCount":16}}}
![\"Schematic](\"/por/images/Reports/POR/2024/2129469/2129469_10784477_1707263931540_RPtag_Capture--rgov-214x142.jpg\")
![\"Biodistribution](\"/por/images/Reports/POR/2019/1720789/1720789_10496721_1555443670440_NSFImage--rgov-214x142.jpg\")