This technology includes the use of engineered human induced pluripotent stem cells (iPSCs) for various applications such as studying cell differentiation, drug screening, and gene transfer therapy. It employs gene targeting donors flanked by DNA sequences compatible with endogenous loci to integrate transgenes through homologous recombination. A key aspect is the flexible gene targeting donor design, used in conjunction with safe harbor transcription activator-like effector nucleases (TALENs).

This technology includes a number of dimeric RGD peptides which been developed and labeled with various PET isotopes (1BF, 68Ga, and 64Cu) for imaging integrin expression in cancer, inflammation, rheumatoid arthritis, myocardial infarct, stroke and traumatic injury. A number of these peptides have been translated into clinic for diagnosis and therapy response monitoring.

This technology includes p300 KO HEK293T cells using crispr/cas9 mediated gene editing technology to be used for various research applications. We showed that p300 deficient cells have impaired glycolysis and are hypersensitive to glucose depletion-induced cell death. p300 is one of major transcriptional co-activators that regulates gene transcription as a histone acetyltransferase. Recent studies reveal that it functions as "writer" for a variety of lysine acylations, including acetylation, crotonylation, butryrylation, 2- hydroxyisobutyrylation, and succinylation.

This technology includes novel compounds which can be expected to selectively target the 5HT6 receptor, which is implicated in CNS-related diseases. In particular 5HT6 antagonism has been implicated in cognitive impairment, AD/PD and drug abuse/alcohol abuse related disorders. 5HT6 compounds have also shown to reduce appetite and induce weight loss. As such, compounds that can selectively antagonize 5HT6 along with an additional signaling pathway implicated in such diseases like inducible nitric oxide synthase (iNOS) may be valuable for such CNS mediated diseases.

This technology includes a blood flow imaging method that allows for a higher density of smaller particles to be detected. Current imaging methods that are based on Doppler measurements are limited by the discontinuity in the capillary flow in the space between red blood cells. The core technology is to use a scattering agent to enhance capillary flow or microcirculation. This technology has been tested for optical coherence Doppler tomography, but can be expended to any Doppler based flow imaging techniques such as laser speckle imaging.

Summary: 
Investigators at the National Institute on Drug Abuse seek co-development partners and/or licensees for collection of mu opioid receptor (MOR) agonists as alternatives for existing compounds.

Description of Technology: 
Although existing opioids are excellent analgesics and useful as positron emission tomography (PET) radiotracers, they come with debilitating side effects. These include addiction, respiratory distress, hyperalgesia, and constipation. Therefore, there is a need for alternatives with lower adverse effects.

Nuclear medicine is the second largest source of medical radiation exposure to the general population after computed tomography imaging. Imaging modalities utilizing nuclear medicine produce a more detailed view of internal structure and function and are most commonly used to diagnose diseases such as heart disease, Alzheimer’s and brain disorders. They are used to visualize tumors, abscesses due to infection or abnormalities in abdominal organs.

About half of the per capita dose of radiation due to medical exposures is provided by computed tomography (CT) examinations. Approximately 80 million CTs are performed annually in the United States. CT scans most commonly look for internal bleeding or clots, abscesses due to infection, tumors and internal structures. Although CT provides great patient benefit, concerns exist about potential associated risks from radiation doses – especially in pediatric patients more sensitive to radiation.

The Transforming Growth Factor Beta (TGF-ß) ligands (i.e., TGF-ß1, -ß2, -ß3) are key regulatory proteins in animal physiology. Disruption of normal TGF-ß signaling is associated with many diseases from cancer to fibrosis. In mice and humans, TGF-ß activates TGF-ß receptors (e.g., TGFBR1), which activates SMAD proteins that alter gene expression and contribute to tumorigenesis.  Reliable animal models are essential for the study of TGF-ß signaling.