Abstract: The present disclosure is directed to genetically modified carrier/donor cells that are engineered to be resistant to its oligonucleotide payload, and methods of delivering an oligonucleotide into a target cell. The disclosure is also directed to methods of treating cancer using the engineered carrier cells of the disclosure. An aspect of this disclosure is directed to engineering carrier cells to be resistant to the detrimental effects of an oligonucleotide.

Abstract: A method of treating cancer in vivo includes introducing in vitro into human mesenchymal stem cells (hMSCs) at least one type of inhibitory oligonucleotide, and contacting a tumor tissue of syncytial cancer cells with the hMSCs in vivo under conditions permitting a hMSC to form a gap junction channel with a first syncytial cancer cell of the tumor tissue. As a result, the at least one type of inhibitory oligonucleotide is delivered into the first syncytial cancer cell by traversing the gap junction channel and the at least one type of inhibitory oligonucleotide is delivered into a second syncytial cancer cell of the tumor tissue by traversing a gap junction channel between the first syncytial cancer cell and the second syncytial cancer cell.

Abstract: The present disclosure relates to methods and compositions for modulating the activity of KCNQ channels as a means for reducing the effects of aberrant KCNQ channel function associated with epilepsy, deafness and arrhythmias including but not limited to, Long-QT syndrome (“LQTS”), and atrial fibrillation. The present disclosure also relates to the discovery of certain regions of KCNQ channels that interact with various channel stimulating molecules such as, ATP, and PIP2, as well as KCNQ channel domains that effect voltage dependant channel activation. The disclosure is also directed to the use of small molecules to modulate KCNQ channel activity in a cell. Moreover, the present disclosure relates to the therapeutic effects of treating a subject with modulators of KCNQ channel activity.

Abstract: It is demonstrated that hyperpolarization-activated cyclic nucleotide-gated (HCN)-based biological pacing, especially that achieved by transduction of the HCN2 gene into cardiac cells in vivo, was significantly improved by co-transduction of the skeletal muscle sodium channel 1 (SkMI) gene. Expression of both genes hyperpolarized the action potential (AP) threshold. When viral biological pacemaker constructs carrying genes for HCN2 and SkMI were injected into the heart of dogs in vivo, the pacemaker function was facilitated by the slow depolarizing HCN2 current and the hyperpolarized AP threshold generated by SkMI. This dual gene therapy provided both highly efficient pacing and a brisk autonomic response that is superior to those of previously developed gene- or cell-based approaches.

Abstract: The present disclosure relates to methods and compositions for modulating the activity of KCNQ channels as a means for reducing the effects of aberrant KCNQ channel function associated with epilepsy, deafness and arrhythmias including but not limited to, Long-QT syndrome (“LQTS”), and atrial fibrillation. The present disclosure also relates to the discovery of certain regions of KCNQ channels that interact with various channel stimulating molecules such as, ATP, and PIP2, as well as KCNQ channel domains that effect voltage dependant channel activation. The disclosure is also directed to the use of small molecules to modulate KCNQ channel activity in a cell. Moreover, the present disclosure relates to the therapeutic effects of treating a subject with modulators of KCNQ channel activity.

Abstract: The present disclosure relates to methods and compositions for modulating the activity of KCNQ channels as a means for reducing the effects of aberrant KCNQ channel function associated with epilepsy, deafness and arrhythmias including but not limited to, Long-QT syndrome (“LQTS”), and atrial fibrillation. The present disclosure also relates to the discovery of certain regions of KCNQ channels that interact with various channel stimulating molecules such as, ATP, and PIP2, as well as KCNQ channel domains that effect voltage dependant channel activation. The disclosure is also directed to the use of small molecules to modulate KCNQ channel activity in a cell. Moreover, the present disclosure relates to the therapeutic effects of treating a subject with modulators of KCNQ channel activity.

Abstract: The present disclosure relates to methods and compositions for modulating the activity of KCNQ channels as a means for reducing the effects of aberrant KCNQ channel function associated with epilepsy, deafness and arrhythmias including but not limited to, Long-QT syndrome (“LQTS”), and atrial fibrillation. The present disclosure also relates to the discovery of certain regions of KCNQ channels that interact with various channel stimulating molecules such as, ATP, and PIP2, as well as KCNQ channel domains that effect voltage dependant channel activation. The disclosure is also directed to the use of small molecules to modulate KCNQ channel activity in a cell. Moreover, the present disclosure relates to the therapeutic effects of treating a subject with modulators of KCNQ channel activity.

Abstract: The present invention relates to methods and compositions for modulating the activity of two-pore domain K+ channels (“K2P channels”) as a means for inducing preconditioning protection. Such preconditioning can be used to reduce the effect of ischemia associated with ischemic heart disease, myocardial infarction or cardiac surgery. The invention is based on the discovery that the myoprotective current induced by short periods of ischemia is carried by a non-classical two-pore domain K+ channel.

Abstract: The invention features an optically-controlled biological device that includes a biological component comprising a non-excitable cell expressing a light-gated ion channel protein and capable of forming gap junction channels with a target cell, and an optical stimulation unit.

Abstract: A device and method for analyzing cells includes a housing with a chamber, a barrier supported by a frame disposed within the chamber, and a plate arranged at a bottom surface of the housing interior of the chamber. The plate is adapted to receive and sustain cells and the barrier separates the plate into at least two contiguous separate areas. In some embodiments, a thin rubber strip is arranged at the bottom edge of the barrier, which facilitates control of the area in which each cell type is grown, the size of the gap between the cells, and helps prevents over growth of the two cell types on to each other.

Abstract: The invention provides a method of creating an atrioventricular bypass tract for a heart comprising growing mesenchymal stem cells into a strip with two ends, and attaching one end of the strip onto the atrium of the heart, and attaching the other end of the strip to the ventricle of the heart. By this attachment, a tract is created that connects the atrium to the ventricle to provide a path for electrical signals generated by the sinus node to propagate across the tract and excite the ventricle.

Abstract: This invention provides a bypass bridge comprising a tract of gap junction-coupled cells having a first end and a second end, both ends capable of being attached to two selected sites in a heart so as to allow the conduction of a pacemaker and/or electrical signal/current across the tract between the two sites, wherein the cells functionally express a sodium channel. The invention also provides related methods of making the bypass bridge, methods of implanting same in a heart, and methods of treating a disorder associated with an impaired conduction in a subject's heart.

Abstract: A method for treating a subject afflicted with a cardiac disorder, in vivo, comprises (i) inducing differentiation of a progenitor cell, in vitro, to a cardiogenic cell; and (ii) administering a therapeutically effective amount of the cardiogenic cell of step (i) to the subject, thereby treating the cardiac disorder in the subject. This invention further provides related articles of manufacture and methods.

Abstract: The present invention provides a method for testing the efficiency of delivering an inhibitory polynucleotide to a target cell or tissue. The invention also provides a method for testing efficiency of delivering and efficacy for an effect on tumor size of an inhibitory polynucleotide against a target gene.

Abstract: This invention provides a bypass bridge comprising a tract of gap junction-coupled cells having a first end and a second end, both ends capable of being attached to two selected sites in a heart so as to allow the conduction of a pacemaker and/or electrical signal/current across the tract between the two sites, wherein the cells functionally express a sodium channel. The invention also provides related methods of making the bypass bridge, methods of implanting same in a heart, and methods of treating a disorder associated with an impaired conduction in a subject's heart.

Abstract: This invention provides methods for determining the ability of a gene construct to alter the rhythm and contractility of a syncytial cell. Furthermore, this invention provides methods for constructing a gene construct capable of altering the rhythm or contractility of a syncytial cell. Finally, this invention provides a method for constructing a gene construct capable of coupling to a syncytial cell.

Abstract: A method of delivering an oligonucleotide or a plasmid expressing an oligonucleotide into a target cell comprises introducing an oligonucleotide into a donor cell, particularly a stem cell, and contacting the target cell with the donor cell under conditions permitting the donor cell to form a gap junction with the target cell, whereby the oligonucleotide or a product of the oligonucleotide is delivered into the target cell from the donor cell.

Abstract: The present invention provides methods and compositions relating to the labeling of target cells with nanometer scale fluorescent semiconductors referred to as quantum dots (QDs). Specifically, a delivery system is disclosed based on the use of negatively charged QDs for delivery of a tracking fluorescent signal into the cytosol of target cells via a passive endocytosis-mediated delivery process. In a specific embodiment of the invention the target cell is a stem cell, preferably a mesenchymal stem cell (MSC). Such labeled MSCs provide a means for tracking the distribution and fate of MSCs that have been genetically engineered to express, for example, a hyperpolarization-activated cyclic nucleotide-gated (“HCN”) channel and administered to a subject to create a biological pacemaker. The invention is based on the discovery that MSCs can be tracked in vitro for up to at least 6 weeks.

Abstract: A method of creating an atrioventricular bypass tract for a heart comprises growing mesenchymal stem cells into a strip with two ends, attaching one end of the strip onto the atrium of the heart, and attaching the other end of the strip to the ventricle of the heart, to create a tract connecting the atrium to the ventricle to provide a path for electrical signals generated by the sinus node to propagate across the tract and excite the ventricle.

Abstract: The present invention relates to expression of CXCR4 in mesenchymal stem cells (MSCs) and homing of MSCs to sites of injury. In particular, the invention provides expanded cultures of MSCs which maintain cell surface expression of CXCR4. The MSCs are capable of homing to sites of injury and are suitable for treatment of ischemic disorders, including cardiac disorders, bone and cartilage disorders, liver disorders, inflammatory disorders, and stroke.