Category Archives: Biomedical Research Tools

Animal models, antibodies, cell lines, reagents, vectors, etc.

Differentially Expressed in Squamous Cell Carcinoma Gene 1

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Summary:

Researchers at The Ohio State University have provided a novel method for diagnosing and treating squamous cell carcinoma and prostate cancer. This invention is based upon the detection of a specific gene (serine protease gene) encoding a human protein called Differentially Expressed in Squamous Cell Carcinoma Gene-1 or “DESC1″. The invention also provides for DESC1 vectors, host cells, antibodies directed to DESC1 polypeptides, hybridization probes, and primers useful in the method of detecting DESC1 mRNA.

Squamous cell carcinoma is the second most common form of skin cancer. This condition is typically diagnosed by visual examination of the morphological characteristics (shape, form, arrangement, etc.) of tissue samples by a cytologist or pathologist. The potential for human error inherent in these methods has thus made it desirable to develop more reliable and efficient techniques. Investigation into the underlying genetics of the disease has led to the identification of several genes of interest. The DESC1 gene, for instance, is expressed in significant levels in epithelial tissues of the head, neck, oral mucosa, tonsils, prostate, testes, and skin in healthy individuals. However, the gene is repressed in squamous cell carcinoma of the head, neck, prostate, and testes, as compared to normal tissue specimens. It has also been determined that DESC1 is not expressed in colon carcinoma, lung carcinoma, melanoma, or HeLa cells. This gene may prove a useful marker for the detection and treatment of squamous cell carcinoma and other skin cancers.

Potential Applications:

  • Diagnosing squamous cell carcinoma, prostate cancer, and other epithelial cancers in a tissue sample.
  • Therapeutic gene to treat squamous cell carcinoma, prostate cancer, and other epithelial cancers.

Advantages:

  • Differential expression of DESC1 permits a novel and improved method for diagnosing squamous cell and prostate carcinoma without the need for visual examination.
  • Expression of DESC1 can be determined using conventional procedures.
  • Down regulation of DESC1 during the progression of squamous cell carcinoma may provide a basis for therapeutic targets.

Yeast Artificial Chromosomes (YAC) Containing Entire Transcript Unit of Human AFGF

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Summary:

cDNA and sequence, newt FGFR2 cDNA and sequence, newt FGFR3 cDNA and sequence, newt KGFR cDNA and sequence, and CHO-KL cell line (KPTr2-2) expressing newt KGFR. Mutant cell lines (Tr31-5-1 and Tr33-1-2) that become non-responsive to aFGF stimulation are used to differentiate biological activities among different forms of aFGF and other FGF proteins. These novel sequences and cell lines substantially enhance the availability of newt acidic fibroblast growth factor and are useful for producing compositions for promoting growth and/or wound healing.

Potential Applications:

Treatment of acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS)

Advantages:

  • Possible cloning of tumor suppression gene
  • Promote growth and/or wound healing

Modified Serial Analysis of Ribosomal Sequence Tags (mSARST)

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Summary:

Knowledge of bacterial diversity is a critical step in understanding and manipulating microbial communities and processes, ranging from environmental bioremediation to improving human health. Researchers at The Ohio State University have significantly improved a novel method for rapidly and comprehensively analyzing bacterial diversity. Serial Ribosomal Sequence Tags (SARST) is a newly described method of examining microbial diversity, and we have developed a modified version of SARST (mSARST) that greatly improves the efficacy of the approach. Both methods use a series of enzymatic reactions to produce concatemers of ribosomal sequence tags that can be cloned sequenced, but mSARST can be readily adapted to a kit-based format and offers up to a 20-fold increase in throughput over traditional clone libraries. To our knowledge, mSARST is also the only cloning technology available to provide both qualitative and quantitative information about the structure of microbial communities, in a high throughput format.

Potential Applications:

  • Characterization of any type of microbial community irrespective of the level of complexity.
  • Comprehensive studies of human gastrointestinal microbiology in support of the prediction and diagnosis of illness and disease.
  • Comprehensive analysis and monitoring of the temporal or spatial changes in microbial diversity in complex natural and managed microbial communities, for quality control and quality assurance purposes.
  • Fundamental studies of microbial ecology.

Advantages:

  • Provides more detailed, rapid and cost effective analysis of bacterial diversity and community structure than previously possible.
  • Offers up to 20-fold increase in throughput over traditional clone libraries.
  • Bias and chimera formation associated with PCR-based analysis is minimized.
  • RSTs can be used to design microarrays for further analysis.
  • Procedure can be packaged into a commercial reagent kit.

Methods for Identifying Nucleic Acid Mutations using Mismatch Modification

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Summary:

Researchers at The Ohio State University have developed a method for the rapid and efficient identification of genetic alterations within large fragments of DNA (>3.2 Kb). Genetic alterations form the basis of many cancers and all inherited diseases. In cancer, there is growing evidence that identification of genetic mutations in the early stages of disease could lead to early interventional treatments that have a greater potential to reduce the morbidity and mortality caused by end-stage disease. This method describes a novel procedure to detect mutated DNA using chemical modifications that carry an easily detectable, antigenic marker. These components can be packaged into a molecular diagnosis kit resulting in rapid, efficient and sensitive detection of genetic mutations. Mutations can then be analyzed to determine the degree to which they are disease-related as well as providing a basic research tool for genetic studies. There is a clear need for the development of rapid, reliable, and sensitive methods for detecting point mutations in nucleic acids. It is anticipated that this technology will provide significant improvements to the interdisciplinary fields of mutation detection and genetic screening.

Potential Applications:

  • Early detection and diagnosis of genetically linked diseases.
  • Provides a basic research tool for the study of genetic mutations.

Advantages:

  • It’s non-radioactive, utilizes no harsh or dangerous chemicals, is conducted within a single tube, is extremely rapid, screens tremendously large fragments of DNA and can easily be adapted to automated formats.
  • This method allows for mutations to be identified and segregated from the overwhelming amounts of normal DNA.

A new carbon based electrochemical detector electrode method of making and uses

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Summary:

Researchers at the Ohio State University have discovered a novel way of making electrochemical detector electrodes with an amperometric glassy carbon electrode system. As opposed to traditional pH detector electrodes, these glassy carbon electrodes are made to withstand chemical attacks and remain stable across a large range of pressure, temperature, and pH conditions. Traditional detector electrodes can also be difficult to miniaturize, must be read by expensive meters, not mechanically robust, and can be potentially dangerous when used for food testing in the human body. The glassy carbon electrode system overcomes all the above limitations. Potential uses of these electrodes include industrial process control, analytical chemistry, biomedical monitoring including blood glucose testing, and medical diagnosis.

Potential Applications:

  • Industrial process control
  • Analytical chemistry
  • Biomedical monitoring
  • Medical diagnosis

Advantages:

  • Can withstand large range of pressure, temperature, and pH conditions
  • Easy to miniaturize
  • Mechanically robust
  • Safe to use inside the human body

A Method for Identifying the Sequence of CyclicPeptides

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Summary:

OSU researchers have developed a method for identifying the sequence of cyclic peptides in an inexpensive, rapid and accurate method. Cyclic peptides provide attractive lead compounds for drug discovery and excellent molecular probes in biomedical research but are difficult sequence by normal methods. Cyclic peptides are typically synthesized on beads and then ones that react with target sites are identified using split and pool technology. The OSU method segregates the bead into an inner and outer layer. The outer layer contains the cyclic peptide and the inner layer contains an identically sequenced linear peptide that can be easily sequenced using Edman degradation and mass spectrometry.

Potential Applications:

Drug discovery and molecular probe

Advantages:

  • Ease of sequencing the cyclic peptide
  • Use of common methods to sequence
  • Can be done more rapidly than current methods
  • Leaves the cyclic peptide intact

Digital Method for Real-Time Frequency Evaluation of Periodic Signals

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Summary:

Frequency counters typically count a frequency of a periodic signal by setting a set gate level. Each time the periodic signal crosses the gate level an event is generated. After calculating the number of events per second, the frequency is then calculated from the periodic signal. Unfortunately, this universal method has not demonstrated stability for frequency measurements. At The Ohio State University, we have created a reliable digital real-time method that detects frequency of a force signal from a microcantilever sensor in Magnetic Resonance Force Microscopy. Additionally, this method demonstrates sensitivity limited only by the displacement noise of a cantilever. Our high precision evaluation of the frequency of a periodic signal can be used as an extra option for any currently available digital signal processing hardware. A prototype is available for testing and evaluation under a confidentiality agreement.

Potential Applications:

  • Detection of biohazards at sensitive immigration and import/export points and at transportation sites
  • Counter intelligence and eavesdropping
  • Breathalizers
  • Any SFM system, MRFM, MRI, and microwave signals

Advantages:

  • Measures frequency shifts of resonator cantilever quickly thus offering increased sensitivity.
  • Continuously measures rather than sampling because it measures in small forces that are 6-7 magnitudes larger than what needs to be measured.
  • Accurately and directly calculates the frequency from the amplitude and the phase of an input signal.
  • The frequency signal is based upon a number of points less than the period of a signal.
  • Enables higher force sensitivity for force microscopy systems and for noise where force is detected through its influence upon the frequency of the oscillating mechanical force detector (microcantilever).
  • Solves the problem of limited bandwidth of amplitude detection.
  • Most effective sound frequency range is DC-1MHz.
  • One can resynchronize by re-inputing data that was taken out of the probe sequence so one can probe the system with the probe sequence.
  • Allows one to create a full MRFM measurement system including a self excitation circuit, a frequency detector, and RF modulation circuits and capable of generating modulation signals whose phase is locked to the cantilever signal.
  • Existing computers already use digital computers.
  • Digital read-out of frequency output time is 4 milliseconds; as computer boards improve, this technique’s speed improves.

Supercritical Carbon Dioxide Method for Embedding High Molecular Weight Biomolecules in Synthetic Polymers

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Summary:

This procedure uses supercritical carbon dioxide to impregnate proteins and other biologically active molecules into a polymethylmethacrylate (PMMA) matrix suitable for tissue engineering and transplant into humans. These materials would achieve greater biocompatibility in physiological enviroments. The exposure to the supercritical carbon dioxide provides simultaneous sterilization and opportunities for the production of foamed morphologies similar to those found in both hard and soft tissues in vivo. This combination of enhanced diffusion, foaming and sterilization can conceivably be exploited to produce or modify a variety of biomedical materials.

Potential Applications:

  • Biomedical implants
  • Cancer treatment

Advantages:

  • Enhanced diffusion
  • Sterilization
  • Function selectivity
  • Low costs

PCR assay to quantify mircoRNA precursors

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Summary:

Today, one technique used to determine if microRNA expression is regulated post transcriptionally is to measure the levels of the precursor and mature microRNA using sensitive PCR. However, microRNA precursors are difficult molecules to quantify by PCR since they have a great deal of secondary structure.

Researchers at OSU have developed a new methodology to amplify and quantify the levels of microRNA precursors using PCR. PCR detection of both precursor and mature microRNA are needed in order to fully understand the degree of post transcriptional regulation that occurs during development and in various diseases.

Potential Applications:

  • Biotechnology supply companies that market PCR reagents, kits and supplies
  • In vitro diagnostic based companies
  • Scientists interested in studying regulation of microRNA biogenesis

Advantages:

  • Sensitive and precise quantification of microRNA precursors.
  • Rapid screening of hundreds of microRNA precursors.
  • When combined with a PCR assay for mature miRNA, can discover microRNAs that are regulated post transcriptionally.

Peptide structure nucleation and enhanced binding by chemical constraint

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Summary:

Stabilized peptide structures can be used to bind to target molecules, such as proteins, to influence biological activity. Researchers at Ohio State University have developed a method by which a stabilzed peptide secondary structure and tertiary contacts can be sythesized simutaneously. The addition of a tertiary contact is not possible using the current methods. The current methods use a intramolecular ring closing methathesis (RCM), while this method uses a intermolecular RCM, allowing for greater control.

Potential Applications:

  • Novel therapuetic synthesis
  • New material sythesises using chemical reactions, such as polymerization depending on functional group added

Advantages:

  • Ability to control functionality with tertiary contact
  • Confer functionality and structure in one reaction