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Zhang H.,Rensselaer Polytechnic Institute | Lee M.-Y.,Solidus Inc. | Hogg M.G.,Solidus Inc. | Dordick J.S.,Rensselaer Polytechnic Institute | Sharfstein S.T.,University at Albany
Small | Year: 2012

A method for high-throughput retroviral transfection of genes and interfering RNA into 3D cell-culture microarrays is described. 3D cultures more closely mimic the in vivo cellular milieu, thus providing cellular responses to genetic manipulation more similar to the in vivo situation than 2D cultures. This technique is applied to transfect several "toxic" short-hairpin RNAs (shRNAs) into 3D cell cultures. It is demonstrated that the toxicity is similar to that obtained by conventional (non-high-throughput) retroviral transfection of cells grown in similar 3D culture microarrays. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zhang H.,Rensselaer Polytechnic Institute | Lee M.-Y.,Solidus Inc. | Hogg M.G.,Solidus Inc. | Dordick J.S.,Rensselaer Polytechnic Institute | And 2 more authors.
ACS Nano | Year: 2010

Three-dimensional (3D) cellular assays closely mimic the in vivo milieu, providing a rapid, inexpensive system for screening drug candidates for toxicity or efficacy in the early stages of drug discovery. However, 3D culture systems may suffer from mass transfer limitations, particularly in delivery of large polypeptide or nucleic acid compounds. Nucleic acids (e.g., genes, silencing RNA) are of particular interest both as potential therapeutics and due to a desire to modulate the gene-expression patterns of cells exposed to small-molecule pharmacological agents. In the present study, polyethylenimine (PEI)-coated superparamagnetic nanoparticles (SPMNs) were designed to deliver interfering RNA and green fluorescent protein (GFP) plasmids through a collagen-gel matrix into 3D cell cultures driven by an external magnetic field. The highest transfection efficiency achieved was 64% for siRNA and 77% for GFP plasmids. Delivery of an shRNA plasmid against GFP by PEI-coated SPMNs silenced the GFP expression with 82% efficiency. We further demonstrated that this delivery approach could be used for screening interfering RNA constructs for therapeutic or toxic effects for cells grown in 3D cultures. Four known toxic shRNA plasmids were delivered by PEI-coated SPMNs into 3D cell cultures, and significant toxicities (41-51% cell death) were obtained. © 2010 American Chemical Society.


Lee M.-Y.,Solidus Inc. | Dordick J.S.,Rensselaer Polytechnic Institute | Clark D.S.,University of California at Berkeley
Methods in Molecular Biology | Year: 2010

Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future. We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data. © 2010 Humana Press, a part of Springer Science+Business Media, LLC.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 985.88K | Year: 2012

DESCRIPTION (provided by applicant): Solidus Biosciences, Inc. in partnership with Rensselaer Polytechnic Institute, will focus on further development, validation, and commercialization of its proprietary Transfected Enzyme and Metabolism Chip (or TeamChip) for high-throughput analysis of systematic drug candidate and chemical metabolism and toxicology. The TeamChip is being developed to mimic first-pass metabolism of the human liver and to predict enzyme-specific hepatotoxicity. A library of human cells expressing different combinations of metabolic enzymes on the TeamChip will be prepared by transfecting metabolic genes using a viral delivery system into human cells encapsulated in three-dimensional (3D) matrices (as small as 60 nL) arrayed on a plastic chip. Thus, the reactivity of target compounds with individual human metabolic enzymes or combinations of enzymes in the human liver or other organ types can be assessed and quantified at speeds commensurate with predictive human toxicity assessment of early stage drug candidates and environmental chemicals. The specific aims/milestones of this Phase II STTR proposal are to: 1. Construct recombinant adenoviruses that carry genes for metabolic enzymes from a human liver cDNA library (e.g., representativeCYP450 isoforms and conjugative metabolic enzymes), demonstrate gene transfection on monolayers of Hep3B cells using fluorogenic/luminescent substrates, and measure different levels of adenoviral enzyme expression by Western blot assays. 2. Prepare the TeamChip containing Hep3B cells expressing various combinations of metabolic enzymes and identify metabolic genes whose differential expression affects the cellular response to model compounds. 3. Optimize on-chip cryopreservation protocols for recombinant adenoviruses and transfected Hep3B cells. Demonstrate metabolism-induced toxicity with cryopreserved TeamChips and compare the results with non- frozen counterparts. In vitro technologies that can be used to quickly assess large numbers of compounds for toxicity remain limited. A critical component of safety evaluation is metabolism and toxicology of chemicals (e.g., drug candidates and environmental chemical toxicants), which reflects the susceptibility of chemicals to be metabolized by human metabolic enzymes and the toxicity of parent compounds and their metabolites. Current approaches to chemical safety assessment are costly, time consuming, and use large amounts of compound and large numbers of animals. Thus, there is great potential and opportunity to apply the TeamChip as a safety assessment tool that can be used to evaluate whether and how specific metabolic enzymes contribute to the toxicity of drug candidates and chemical toxicants. This capability may also be used to predict differences among individuals in drug and chemical metabolism and toxicity. PUBLIC HEALTH RELEVANCE: The drug discovery process is an investment-intensive, high-risk endeavor that results in low yields of effective and safe drugs; a problem that is confounded by the significant lack of information that exists in predicting the metabolic fate of drug candidates, in general, and in predicting the reactivity of drug candidates in the human body. The proposed Phase II STTR project for the development of Solidus Bioscience's TeamChip technology has significant relevance to public health by providing pharmaceutical researchers with in vitro information needed to predict the in vivo metabolism of drug candidates, and thus help to decide which compounds are brought forward for leadoptimization and the ultimate development of better and safer drugs. Furthermore, this research is relevant to the prioritization of industrial and environmental chemicals in terms of their safety and use.


Patent
Solidus Inc. | Date: 2013-04-25

Disclosed herein is a microarray cell chip. The microarray cell chip includes an upper substrate that has biomatrices encapsulating biomaterials formed on one surface thereof and through holes penetrating from one surface to the other surface thereof and a lower substrate that is coupled with the upper substrate and is provided with wells storing reagents supplied to the biomatrices. The microarray cell chip according to the present invention can smoothly transfer the culture media and the reagents to the biomaterials embedded in the biomatrices through the diffusion and simply separate the upper substrate from the lower substrate, thereby improving the easiness of washing. Therefore, the present invention provides an environment similar to the bio environment, thereby making it possible to increase accuracy of an experiment.


Kwon S.J.,The Interdisciplinary Center | Mora-Pale M.,The Interdisciplinary Center | Lee M.-Y.,Solidus Inc. | Dordick J.S.,The Interdisciplinary Center | Dordick J.S.,Rensselaer Polytechnic Institute
Current Opinion in Chemical Biology | Year: 2012

The enormous pool of chemical diversity found in nature serves as an excellent inventory for accessing biologically active compounds. This chemical inventory, primarily found in microorganisms and plants, is generated by a broad range of enzymatic pathways under precise genetic and protein-level control. In vitro pathway reconstruction can be used to characterize individual pathway enzymes, identify pathway intermediates, and gain an increased understanding of how pathways can be manipulated to generate natural product analogs. Moreover, through in vitro approaches, it is possible to achieve a diversification that is not restricted by toxicity, limited availability of intracellular precursors, or preconceived (by nature) regulatory controls. Additionally, combinatorial biosynthesis and high-throughput techniques can be used to generate both known natural products and analogs that would not likely be generated naturally. This current opinion review will focus on recent advances made in performing in vitro pathway-driven natural product diversification and opportunities for exploiting this approach for elucidating and entering this new chemical biology space. © 2012 Elsevier Ltd.


Patent
Samsung and Solidus Inc. | Date: 2012-05-17

There is provided a fluid discharging device including: a first pressure generating unit generating a first pressure for discharging a fluid; a second pressure generating unit generating a second pressure for discharging a fluid, and being controllable so as to change a magnitude of the second pressure; and a nozzle discharging the fluid pressurized by the first and second pressure generating units.


Patent
Samsung and Solidus Inc. | Date: 2014-02-12

Disclosed is a cell chip and methods for the use thereof, wherein the cell chip includes a substrate made of an opaque material and having a plurality of insertion holes formed therein, a filler made of a transparent material and inserted into each of the insertion holes so as to protrude from the substrate, and a biomatrix which is formed on the filler and immobilizes a biomaterial. Also, another substrate having a plurality of wells which store a fluid is further provided thus forming a 3D cell chip.


Trademark
Solidus Inc. | Date: 2017-01-11

computer software for building e-commerce applications; computer software to extend functionality of open source computer software for building e-commerce applications.


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