Abstract: The present invention provides compositions and methods of making and using novel MYC mRNA antisense inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of a condition (e.g., cancer).

Abstract: The present invention provides compositions and methods of making and using MYC mRNA antisense inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of a condition (e.g., cancer).

Abstract: The present invention provides compositions and methods of making and using novel MYC mRNA antisense inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of a condition (e.g., cancer).

Abstract: A power lock actuator is provided for a door lock mechanism of a vehicle. The actuator includes an electric motor, a linear drive, and a slip clutch between the motor and the linear drive. The clutch includes a dual-lobe pinion for pulsed energy transmission from the motor to the linear drive, to provide soft starts and stops, which extend the life of the drive assembly 26. The linear drive includes a screw with multiple, discontinuous male thread segments to minimize friction with female threads on the extendible and retractable carriage, thereby minimizing wear between the screw and the carriage.

Abstract: The present invention provides compositions and methods of making and using microRNA inhibitors. In a particular embodiment, the invention features compositions and methods useful for the treatment of diseases, including neoplasia (e.g., breast cancer).

Abstract: A power locking pull or push button handle assembly is provided for a vehicle door having a lock and a latch. The handle assembly includes a base with a housing. A handle is pivotally mounted on the base, a power lock assembly is mounted within the housing on the base, and a keypad on the handle is operatively connected to the power lock assembly for keyless unlocking of the door. The handle includes a cover and backbone secured together, with the keypad sandwiched between the cover and backbone. The keypad is reinforced with a steel plate. Loads on the handle are shared by the backbone, cover, and keypad.

Abstract: A power lock actuator is provided for a door lock mechanism of a vehicle. The actuator includes an electric motor, a linear drive, and a slip clutch between the motor and the linear drive. The clutch includes a dual-lobe pinion for pulsed energy transmission from the motor to the linear drive, to provide soft starts and stops, which extend the life of the drive assembly 26. The linear drive includes a screw with multiple, discontinuous male thread segments to minimize friction with female threads on the extendible and retractable carriage, thereby minimizing wear between the screw and the carriage.

Abstract: A power locking pull or push button handle assembly is provided for a vehicle door having a lock and a latch. The handle assembly includes a base with a housing. A handle is pivotally mounted on the base, a power lock assembly is mounted within the housing on the base, and a keypad on the handle is operatively connected to the power lock assembly for keyless unlocking of the door. The handle includes a cover and backbone secured together, with the keypad sandwiched between the cover and backbone. The keypad is reinforced with a steel plate. Loads on the handle are shared by the backbone, cover, and keypad.

Abstract: Compounds comprising a diagnostic or therapeutic moiety can be retained inside a cell by conjugating the moiety to at least one PNA that is targeted to the transcripts from a gene of interest. The diagnostic or therapeutic moiety is also conjugated to at least one targeting moiety specific for an extracellular receptor or other cell surface molecule. The targeting moiety binds to the surface of a cell, and the entire compound is then internalized. Once inside the cell, the PNA portion of the diagnostic or therapeutic compound binds to RNA transcripts in a sequence specific manner. Binding of the PNA to its target RNA transcript retains the compound within the cell. The PNA can be designed to bind to a predetermined nucleic acid sequence from an RNA transcript, for example a mutated or overexpressed sequence that is characteristic of a pathological state.

Abstract: The present invention is directed to implants that include therapeutic molecules bonded to their surfaces. The therapeutic molecules interact with cells that are adjacent, near, or adhering to the implant. The covalently-bonded therapeutic molecules may be released from the implant surface by changes in pH or enzymes characteristic of cells adjacent to the implant. Preferably the covalently-bonded agents include an antibiotics that are released from the implant surface by bacteria and in this way ensures that the antibiotic is released at sites on the implant that would serve as centers for both bacterial colonization and biofilm formation.

Abstract: Compounds comprising a diagnostic or therapeutic moiety can be retained inside a cell by conjugating the moiety to at least one PNA that is targeted to the transcripts from a gene of interest. The diagnostic or therapeutic moiety is also conjugated to at least one targeting moiety specific for an extracellular receptor or other cell surface molecule. The targeting moiety binds to the surface of a cell, and the entire compound is then internalized. Once inside the cell, the PNA portion of the diagnostic or therapeutic compound binds to RNA transcripts in a sequence specific manner. Binding of the PNA to its target RNA transcript retains the compound within the cell. The PNA can be designed to bind to a predetermined nucleic acid sequence from an RNA transcript, for example a mutated or overexpressed sequence that is characteristic of a pathological state.

Abstract: The K-RAS oncogene is a member of the highly conserved RAS gene family, whose protein products are believed to play a significant role in signal transduction and the regulation of cellular proliferation. Mutation-activated K-RAS is found in 30-50% of both advanced and early stage ovarian cancers. The present invention relates to a method for modulating mutation-activated K-RAS expression in ovarian, colon, lung, thyroid, prostate, skin, and hematologic cancer cells by administering an effective amount of an oligonucleotide targeted against a portion of mRNA for human K-RAS. Oligonucleotides are provided that are specifically hybridizable with mRNA encoding mutation-activated human K-RAS. Such oligonucleotides can be used for therapeutics and diagnostics as well as for research purposes. The present invention further encompasses pharmaceutical compositions comprising the antisense oligonucleotides of the invention.

Abstract: Oligodeoxynucleotides complementary to genomic RNA of a negative-stranded nonsegmented RNA virus are provided. Methods of inhibiting infection of cells by a negative-stranded nonsegmented RNA virus and treating animals infected with a negative-stranded nonsegmented RNA virus using these oligodeoxynucleotides are also provided.

Abstract: Peptide nucleic acid (PNA) oligomers are conjugated to a ligand which is capable of binding to a cell surface receptor. The ligand facilitates cellular uptake of the PNA oligomer. Where the ligand is a peptide, the conjugate may be produced as a unitary molecule by first synthesizing the peptide ligand by solid phase or solution peptide synthesis, followed by synthesis of the PNA oligomer as an extension of the peptide ligand. The PNA oligomer base sequence is selected to hybridize to a target polynucleotide sequence by either triplex (dsDNA) or duplex (ssDNA; RNA) formation.

Abstract: A vector containing a selected nucleic acid sequence interposed between the terminal ends of a Tn7 transposon and a method for site specific integration of genetic material into a chromosome using those vectors are provided.

Abstract: The present invention provides a method for producing an oligonucleotide having stereospecific substituted phosphonate linkages by use of a pentavalent Grignard coupling reaction on a solid phase support. The method can be used for automated synthesis of oligonucleotides having sequential equatorial or axial stereospecific substituted phosphonate linkages.