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Technologies

Description:

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.   

Benefits:

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.

Potential Applications:

  • Delivery of insulin with minimal invasiveness.
  • Paired with a non-invasive blood glucose monitor, this depot could potentially be used as a non-invasive automatic blood glucose control system.

IP Status:

Patent Pending

Description:

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.

Benefits:

  • Low cost.
  • Easy to use.
  • Combines the power of smartphones and ubiquity of cellular infrastructure, Quick Response (QR) codes and national identification cards.
  • QR codes encode 400 times more data than UPC codes, can tolerate up to 30% damage and still have fast readability.  

Jeev (PDF)

Brief Description:

A new method to analyze RNA lariats by employing the high-throughput sequencing of purified RNA lariat populations. 

Invention Description:

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.  

Advantages:

· 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.

IP Status:

Patent Pending

Brief Description:

A biocompatible polymer bone cement with numerous advantages over the currently used polymethyl methacrylates.

Background:

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.

Invention Description:

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.

Uses:

  • Bone repair
  • Orthopedic surgeries
  • Implants, etc.

Advantages:

  •  Biocompatible
  •  Less heat generated during polymerization
  •  High strength
  •  Low shrinkage

 *Patent Pending

Chemically Initiated Bone Cement (PDF)

Brief Summary:

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.

Detailed Description:

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.

Uses:

  •  To generate large numbers of osteocyte-like cells in order to produce sufficient quantities of osteocytes for study.
  •  To generate large numbers of cells of a homogeneous stage of osteogenic differentiation.
  •  To study osteocyte secretion of sclerostin, such as screening for sclerostin antagonists.
  •  To investigate regulation of FGF23 expression in osteocytes and the role of osteocytes in regulation blood calcium/phosphate homeostasis.
  •  To study the role of osteocytes as mechanosensory cells and their role in regulating bone response to mechanical stress.
  •  To screen potential new therapies to induce bone formation.
  •  To track cells responsible for bone formation in vivo.
  •  To identify additional osteocyte-selective markers and receptors.

Advantages:

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.

Investigators: 

Bonewald, Lynda  F.; Woo, Stacey M.

Bone Formation Cell Lines (PDF)

Description:

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.

Uses:

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).

Advantages:

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.

Investigators: 

Dallas, Sarah L.; Bonewald, Lynda F.; Lu, Yongbo; Kamel, Suzan A.

Collagen Assembly Cell Line (PDF)

A drug delivery system that overcomes the problems associated with P-glycoprotein mediated drug efflux.

Disadvantages of Current Treatments:

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.  

Invention Details:

In response to these troublesome efflux issues, UMKC researchers have developed methods of:

  • Converting drugs that are substrates for the P-gp transporter into derivatives not recognized by P-gp as substrates, preferably targeted to and recognized by an influx membrane transporter/receptor (such as a peptide, vitamin or other nutrient transporter). The efflux of such derivatives from cells by the P-gp transporter is thereby eliminated or substantially reduced while their transport into target cells by one or more influx transporters/receptors can be effectively enhanced increasing the bioavailability of bioactive compounds that are P-gp substrates.
  • Increasing the concentration of bioactive compounds that are P-gp substrates in sanctuary sites of a mammalian subject.
  • Enhancing cellular delivery of bioactive compounds that are P-gp substrates.  

Suggested Uses:

For use with various anticancer drugs, anti-HIV drugs, calcium channel drugs and other drugs which are substrates limited by this efflux transporter.  

Advantages:

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

Drug Delivery (PDF)

Antiviral compounds that can reach the anterior segment and/or the vitreo-retinal segment of the eye when administered either topically or systemically to improve the treatment of viral infections such as the herpes group of viruses.

Need:

A need exists for antiviral compounds that are sufficiently hydrophilic to be formulated into solutions such as eye drops and are efficacious when applied topically to the eye. A need also exists for antiviral compounds that reach both the anterior segment and the vitreo-retinal segment or the retina of the eye when administered systemically.

Disadvantages of Current Treatments:

Infections with the herpes simplex virus can lead to severe corneal scarring and opacity. The currently available therapy for HSV keratitis involves the use of a 1% trifluorothymidine (TFT) solution. However, one of the major problems associated with TFT therapy is cytotoxicity, which restricts its use in long-term treatment. Due to problems associated with the use of ointments in the eye, acyclovir (ACV) ointment has not been approved for clinical use in HSV keratitis patients in the United States. In addition, ACV ointment is not effective against stromal keratitis or when the deeper ocular tissues are involved, suggesting that ACV has poor permeation characteristics across the corneal epithelium. The corneal epithelium is composed of 5 to 6 layers of columnar epithelium with tight junctions, making paracellular diffusion across this epithelium minimal. Beneath the epithelial layer is the stroma, which contains more than 90% water, and hence presents a barrier to hydrophobic compounds.    

Invention Details:

UMKC professor Dr. Ashim K. Mitra has developed esters with sufficient hydrophilicity to be formulated into pharmacologically active compositions, such as aqueous solutions (e.g., eye drops). Compounds of the invention can be effectively transported into the ocular tissues. Specifically, such compounds effectively reach the anterior segment and/or the vitreo-retinal segment when administered either topically or systemically. The compounds formulated have been shown to be effective against viral infections, particularly the herpes group of viruses (e.g., herpes simplex types 1 and 2, varicellazoster virus (VZV) and human cytomegalovirus (HCMV)). The present compounds employ oligopeptide transporters for delivery to the deeper tissues of the cornea. Thus, the present compounds are effective in cases where the corneal stromal and underlying tissues have been infected. These compounds have shown excellent in vitro antiviral activity against HSV 1 in HFF cells and in vivo rabbit epithelial keratitis with no significant cytotoxicity.

Suggested Uses:

  • Ophthalmic drug delivery
  • HCMV treatment
  • Herpes simplex treatment
  • VZV treatment    

Advantages:

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

Antiviral Eye Compounds (PDF)

Need:

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. 

Invention Details:

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.

Advantages:

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.

Suggested Uses:

To treat liver fibrosis as well as other diseases in which IGF2R plays an important role.

Patent Pending

IGF2R Peptide Ligands (PDF)

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.

Need:

Oligonucleotides have been of great interest to research and pharmaceutical industries for their ability to modulate various gene targets by inhibiting/modifying protein translation. The major downfall of current oligonucleotides is that they are chemically unstable and degrade quickly when administered as a drug or exposed to high temperatures.

Invention Details:

This invention describes new oligonucleotide analogs called PNAs, which are resistant to degradation and can be directly conjugated to gene targets, siRNAs and other oligonucleotides for therapeutic and imaging purposes. These novel PNAs have the potential to alleviate many of the current disadvantages of RNA-based therapies used in the clinic today.

Advantages:

This new class of PNAs have potent RNA silencing capabilities that are potentially more resistant to temperature and enzymatic degradation in the body than current technology.

Suggested 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

Technology Summary (PDF)

UMKC inventors have discovered that administering β-aminoisobutyric acid to an inactive individual preserves bone homeostasis and prevents deterioration of bone and other tissues of the musculoskeletal system.

Need:

As the population ages, there is an increasing prevalence of musculoskeletal conditions that are becoming a major healthcare burden. Approximately 126.6 million adults suffer from some form of musculoskeletal disease, which accounts for 18% of all office visits, and has caused an estimated 291 million lost work days. The combined economic impact and healthcare costs are estimated at $874 billion or 5.7% GDP. There is a clear unmet need to decrease the healthcare and economic burden associated with musculoskeletal diseases.

Invention Details:

BAIBA is a small molecule myokine that is generated by the catabolism of the amino acid valine during exercise. Studies have demonstrated that BAIBA production increases in the plasma during exercise and decreases many metabolic risk factors. Inventors at UMKC have built upon this data and demonstrated that BAIBA protects osteocytes from cell death caused by the production of reactive oxygen species (ROS). Working through the Mas-Related G-Protein Coupled Receptor, BAIBA was able to prevent mitochondrial breakdown caused by ROS. In an in vivo model for muscle disuse, BABIA administered in the drinking water (100 mg/kg/day) protected mice against bone and muscle loss. This protection is mainly observed in young mice. This data suggests that BABIA administration may prevent muscle and/or bone loss associated with aging and has the potential to help treat musculoskeletal diseases.

Advantages:

Currently, the treatment for many of the musculoskeletal diseases are lacking and are mainly palliative. This technology has the potential to be used to treat painful and debilitating musculoskeletal diseases or prevent further tissue destruction

Suggested Uses:

The invention has the potential to impact therapeutic areas such as:
  • The elderly or to patients that will be immobilized for extended periods of time due to accidents, sports related injuries or illnesses to prevent muscle deterioration.
  • Cancer patients to prevent cachexia.
  • Treatments for osteoporosis.
  • Aid in the treatment of muscular diseases.

Technology Summary (PDF)