A light activated insulin depot that remains inactive until irradiated with light. Once irradiated, the depot can release insulin in a dose dependent manner by varying the time and intensity of light exposure.
This depot could replace current diabetic therapies such as multiple daily injections or the use of an insulin pump. With fewer injections and no cannula, the chance for infection would dramatically decrease. Also, easier dosing and delivery will allow for better patient compliance and easier maintenance of blood glucose levels.
Patent Pending
Jeev is based on a client-server model where the client smartphones and the server smartphone communicate via cheap text messaging. (The messages are encrypted for security reasons.) When a child is first vaccinated, the client smartphone (carried by a health worker) generates and prints a QR code sticker using the child’s and parent’s/ legal guardian’s information. A vaccination record for that child is created on the server. The QR code sticker is affixed to the national ID card of the parent, a necessary form of permanent documentation used in many under-resourced nations. QR uniquely identifies the child without biometric data. Encryption is employed to avoid unauthorized clients from reading the QR codes. Extra stickers are provided to the parent; the code can also be sent as a text message to the parent’s cell phone. This protects the vaccination record in case documentation is lost. During future vaccination visits, the client smartphone scans the QR code on the ID card and the vaccination record is updated on the server. Vaccination coverage information can be visualized by health officials on the server smartphone.
A new method to analyze RNA lariats by employing the high-throughput sequencing of purified RNA lariat populations.
UMKC researchers have developed a new technology for the analysis of RNA lariats called Lariat-seq, which is high-throughput sequencing of purified RNA lariat populations. Lariat-seq can be used to investigate gene structure, identify alternative splicing patterns, map intron RNA branch points, compare gene transcription levels and identify small RNAs encoded within intron lariats. In addition, Lariat-seq can identify the presence of other (non-lariat) covalent modifications in RNAs.
Lariat-seq increases the accuracy of genome annotation and simplifies the process of identifying lariat RNA branch points and the sites of some other covalent modifications of RNA. These advances will speed the development of diagnostics and drugs that target RNA features related to intron splicing as well as RNA covalent modifications that are not due to an RNA branch. Lariat-seq is a very sensitive method for basic and applied researchers to identify introns, branch point sequences, alternative splicing events, as well as the presence of covalent modifications in RNAs that are not due to an RNA branch. The sensitivity can be greatly enhanced by reducing RNA lariat debranching activity in the cells that are the source of the experimental RNA.
· Increased sensitivity
· Increased accuracy
The sensitivity of Lariat-seq is an improvement over other methods for identifying introns and alternative splicing events. Furthermore, Lariat-seq is the only way to globally identify the lariat RNA branch point sequences within a heterogenous RNA population. Current methods require evaluation of one branch point at a time. Lariat-seq is also the only way to globally identify sites of covalent RNA modifications that are not due to an RNA branch within a heterogenous RNA population.
Patent Pending
A biocompatible polymer bone cement with numerous advantages over the currently used polymethyl methacrylates.
Currently available commercial bone cements are based on polymethyl methacrylates and have several disadvantages including toxicity, lack of bioactivity, volumetric shrinkage, tissue necrosis and the generation of heat upon polymerization. Due to these high temperatures produced during polymerization, antibiotic treatment with bone cement is very limited. Only tobramycin, gentamycin and vancomycin are heat-stable and can survive the high temperatures during the polymerization of PMMA's.
Our chemically initiated cement is composed primarily of a monomer that has already proven very effective in commercial dental composites. Our extensive testing of this new cement has found that this system is biocompatible, has a peak exotherm that is below 45 degrees C, low shrinkage and excellent mechanical properties. This system provides a biocompatible alternative to PMMA-based bone cements while maintaining good mechanical properties.
*Patent Pending
UMKC researchers have developed novel cell lines that are useful in the examination of osteocyte function, biomineralization, SOST/sclerostin, FGF23 and other mechanisms of osteoblast-to-osteocyte differentiation.
The two cell lines were isolated from long bone of a mouse that was generated by crossing the Immortomouse® with a mouse where the DMP1 promoter drives expression of the GFP. One of the cell lines, IDG-SW3 (SW3), expresses all of the markers of osteocytes including Dmp1-GFP, Dmp1, E11/gp38, SOST/sclerostin and FGF23. The second cell line, IDG-TI (T1), mainly expresses the characteristics of the matrix producing osteoblast such as high alkaline phosphatase, with delayed expression of Dmp1-GFP and E11/gp38, but no expression of SOST/sclerostin or FGF23. Both cells will produce new bone in vivo.
This invention is an improvement over previous cell lines due to the following factors:
1. The cells are maintained in a non-differentiated state at 33°C in the presence of interferon- g (IFN-g), which allows large scale production without the loss of phenotype as occurs with other cell lines.
2. Upon culture at 37°C in the absence of IFN-g, the temperature-sensitive large T-antigen is no longer expressed, no longer functional and no longer contributes to the cell phenotype. Thus, the cells have the same gene expression as primary cells.
3. The cells are clonal, so all cells are homogeneous and at the same stage of differentiation.
4. The IDG-SW3 cells express the series of markers of the early-to-late osteocyte including Dmp1-GFP, E11/gp38, SOST/sclerostin and FGF23.
5. These cells can be maintained not only in 2D cultures but also in 3D cultures.
6. These cells are viable up to 35-50 days.
7. These cells will generate new bone in vivo.
Bonewald, Lynda F.; Woo, Stacey M.
Immortal cell lines representing the late osteoblast/early osteocyte phenotype that stably express a collagen-GFP or collagen-mCherry fusion protein to fluorescently label type I collagen fibrils either red or green. These novel cell lines allow visualization of collagen fibril assembly in living cells over time, which is not possible with existing technologies.
1. Screening for drugs that enhance collagen assembly and could therefore have potential as bone anabolic treatments for diseases such as osteoporosis.
2. Screening for drugs that inhibit collagen assembly and therefore have the potential to prevent fibrosis, etc.
3. Developing approaches for tissue engineering of bone tissues.
4. Investigating mechanisms of tissue destruction (such as the degradation of matrix proteins by proteases that occurs during inflammation).
These novel cell lines allow for the visualization of collagen fibril assembly in living cells over time, which is not possible with existing technologies. The only other approaches that have been used for monitoring collagen assembly in living cells include using fluorescently labeled antibodies or a fluorescently labeled recombinant bacterial protein. These approaches may potentially interfere with the protein function and only label a population of fibrils at one point in time, which can then be followed (i.e. they do not necessarily label new collagen as it is synthesized). The specificity of the bacterial binding protein for type I collagen as opposed to other collagens is unclear and neither of these probes can be used to follow intracellular steps in the collagen assembly pathway, as they do not cross the cell membrane.
Dallas, Sarah L.; Bonewald, Lynda F.; Lu, Yongbo; Kamel, Suzan A.
P-Glycoprotein (P-gp) is a transport protein that effluxes a wide variety of structurally unrelated drugs out of cells. The bioavailability of various anticancer drugs, anti-HIV drugs, calcium channel drugs and other drugs which are substrates is limited by this efflux transporter. Over-expression of P-gp by tumor cells confers multi-drug resistance. Efflux of many anticancer drugs including taxol, vincristine, vinblastine, actinomycin D, colchicines and daunorubicin, from tumor cells makes P-gp a major barrier to chemotherapy. High expression of this transporter on the blood-brain-barrier (BBB) restricts the entry into the brain of P-gp substrates such as anti-HIV drugs such as ritonavir, saquinavir, nelfinavir and various anticancer drugs, and thus imposes a major challenge in the treatment of various diseases of the brain.
Expression of the efflux transporter on various body tissues and cells not only influences the in vivo disposition of various therapeutically active drugs but also greatly influences the drugs' pharmacokinetics. It has been known that inhibition of P-gp by various modulators can lead to improved bioavailability of drugs across the intestines, the kidneys and the BBB. Various modulators that inhibit P-gp are often co-administered with other bioactive agents to increase bioavailability. However, use of these compounds is limited by their toxicity. To achieve P-gp inhibition, doses that result in high serum concentrations of the toxic inhibitor are required. Although various approaches have been studied to overcome P-gp mediated drug efflux, P-gp remains a major barrier to bioavailability, chemotherapy and effective permeation of P-gp substrates into the brain and other tissues.
In response to these troublesome efflux issues, UMKC researchers have developed methods of:
For use with various anticancer drugs, anti-HIV drugs, calcium channel drugs and other drugs which are substrates limited by this efflux transporter.
Inhibition of P-gp by various modulators can lead to improved bioavailability of drugs across the intestines, the kidneys and the blood-brain barrier. Lower toxicity due to less drugs being administered.
*US Patents 7,910,553; 7,214,664
This technology can reach both the anterior segment and the vitreo-retinal segment or the retina of the eye when administered topically or systemically.
*US Patents 7,553,812; 7,825,086
Liver Fibrosis is caused by chronic diseases such as hepatitis, liver cirrhosis caused by alcohol abuse and nonalcoholic steatohepatitis or fatty liver disease. The prevalence of liver fibrosis is ever-increasing and effects approximately 30 million people in the United States alone. Over 11% of people with liver fibrosis will progress to the more severe condition of cirrhosis, in which the liver begins to decompensate and lose overall function. The fibrotic stage is considered a key inflection point where baseline liver function can still be salvaged with adequate treatment. However, no approved treatment exists that ameliorates or reverses the course of fibrosis.
Liver Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the liver. Hepatic stellate cells (HSCs) are responsible for the excessive production of ECM in a fibrotic liver. A protein found on the surface of HSCs is insulin-like growth factor 2 receptor (IGFR2), which is upregulated in HSCs during liver fibrogenesis. One of the major functions of IGFR2 is to internalize extracellular ligands; therefore, IGFR2 could be used as a delivery system for small molecules into HSCs.
The proposed invention is an IGF2R-binding peptide identified by protein-based and whole-cell-based phage display with high binding affinity and target specificity. The proposed peptide (a.a. sequence - VHWDFRQWWQPS) exhibits high binding affinity and specificity toward IGF2R. The peptide acts via two distinct mechanisms of action, 1.) it acts as a carrier to deliver conjugated small molecule agents to HSCs; and 2.) it acts as a targeting ligand for nanoparticles encapsulating antifibrotic agents.
Conventional methods for delivering drugs to HSCs have limitations, including inefficient uptake. IGF2R is ubiquitously expressed on HSCs and facilitates entry of extracellular molecules at a relatively rapid rate. Identifying peptide ligands that target IGF2R and bind with high affinity is imperative to the development of a HSC-targeted drug delivery system. The identification of the IGF2R-specific peptide can be used to develop targeted therapeutics or imaging agents for liver fibrosis.
To treat liver fibrosis as well as other diseases in which IGF2R plays an important role.
Patent Pending
UMKC inventors have developed proprietary peptide nucleic acid (PNA) sequences capable of forming stable oligonucleotides or small interfering ribonucleic acids (siRNA) that are applicable across a wide range therapeutic and research uses.
The treatment of various diseases including but not limited to cancer, hepatitis, cardiovascular disease, hypertriglyceridemia and muscular dystrophy. In addition, the technology can be used in various molecular imaging techniques such as FISH, ULYSIS and microarrays for research and diagnostic purposes.
Patent Pending