29604results about How to "Strong specificity" patented technology

Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.

Provided are methods and compositions for detecting and treating normal, hypoplastic, ectopic or remnant tissue, organ or cells in a mammal. The method comprises parenterally injecting a mammalian subject, at a locus and by a route providing access to above-mentioned tissue or organ, with an composition comprising antibody / fragment which specifically binds to targeted organ, tissue or cell. The antibody / fragment may be administered alone, or labeled or conjugated with an imaging, therapeutic, cytoprotective or activating agent.

Polymeric delivery devices have been developed which combine high loading / high density of molecules to be delivered with the option of targeting. As used herein, “high density” refers to microparticles having a high density of ligands or coupling agents, which is in the range of 1000-10,000,000, more preferably between 10,000 and 1,000,000 ligands per square micron of microparticle surface area. A general method for incorporating molecules into the surface of biocompatible polymers using materials with an HLB of less than 10, more preferably less than 5, such as fatty acids, has been developed. Because of its ease, generality and flexibility, this method has widespread utility in modifying the surface of polymeric materials for applications in drug delivery and tissue engineering, as well other other fields. Targeted polymeric microparticles have also been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and have targeting ligands directly bound to the microparticle surface. Preferred applications include use in tissue engineering matrices, wound dressings, bone repair or regeneration materials, and other applications where the microparticles are retained at the site of application or implantation. Another preferred application is in the use of microparticles to deliver anti-proliferative agents to the lining of blood vessels following angioplasty, transplantation or bypass surgery to prevent or decrease restenosis, and in cancer therapy. In still another application, the microparticles are used to treat or prevent macular degeneration when administered to the eye, where agents such as complement inhibitors are administered.

Stimulation of one or more neurons of the sympathetic nervous system, including the splenic nerve, to attenuate an immune response, including an inflammatory immune response, is discussed. Devices and systems to stimulate the sympathetic nervous system to attenuate an immune response are also discussed. Devices discussed include pulse generators and drug pumps. Systems are described as optionally having one or more sensors and operator instructions. In specific examples, stimulation of the splenic nerve of pigs with a pulse generator is shown to be safe and effective in attenuating a lipopolysaccharide-induced immune response.

Stimulation of one or more neurons of the sympathetic nervous system, including the splenic nerve, to attenuate an immune response, including an inflammatory immune response, is discussed. Devices and systems to stimulate the sympathetic nervous system to attenuate an immune response are also discussed. Devices discussed include pulse generators and drug pumps. Systems are described as optionally having one or more sensors and operator instructions. In specific examples, stimulation of the splenic nerve of pigs with a pulse generator is shown to be safe and effective in attenuating a lipopolysaccharide-induced immune response.

The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

This invention relates to compounds, compositions, and methods useful for modulating BCL2 gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of BCL2 gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of BCL2 genes (e.g., BCL2, BCL-XL, BCL2-L1, MCL-1 CED-9, BAG-1, E1B-194 and / or BCL-A1). The small nucleic acid molecules are useful in the treatment of cancer, malignant blood disease, polycytemia vera, idiopathic myelofibrosis, essential thrombocythemia, myelodysplastic syndromes, autoimmune disease, viral infection, and proliferative diseases and conditions

This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase (MAP kinase) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MAP kinase gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase (e.g., JNK-1, JNK-2), p38 (MAPK 14), ERK (e.g., ERK-1, ERK-2) and / or c-Jun.

The present invention provides an engineered multidomain protein including at least two nonidentical engineered domains, each of which contains a protein-protein interaction interface containing amino acid sequence segments derived from two or more existing homologous parent domains, thereby conferring on the engineered domains assembly specificities distinct from assembly specificities of the parent domains. In particular, the engineered domains form heterodimers with one another preferentially over forming homodimers. Methods of designing and using the engineered proteins are also included.

The present invention provides methods of directly stimulating neural tissue with optical energy. By stimulating neural tissue at wavelengths, laser pulses, and spot sizes disclosed herein, nerve stimulation may be used to uniquely stimulate neural tissue in way not afforded by other means of stimulation. It can allow basic scientists to study the properties of individual neurons or populations of neurons without piercing tissue with fragile microelectrodes. Furthermore, responses of neural tissue can be studied in a pure fashion without contamination by electrical artifact commonly seen with electrical stimulation. With respect to clinical uses, optical stimulation can be used to map function in subsections of peripheral nerves as an aid to operative repair. Finally, stimulation with optical energy does not require physical contact with the nerve which may be an advantage clinically when physical manipulation of neural tissue is not desired.

Rolling circle replication of a padlock primer is inhibited when it is hybridized to a target nucleic acid that is long or circular. The invention provides methods of addressing this problem including cutting the target nucleic acid near or preferably at the site which hybridizes with the padlock probe, whereby a 3'-end of the cut target nucleic acid acts as a primer for rolling circle replication of the padlock probe. Also included is a method of assaying for a polyepitopic target by the use of two affinity probes each carrying an oligonucleotide tag and of a padlock probe for rolling circle replication in association with the two affinity probes

This invention relates to compounds, compositions, and methods useful for modulating wingless (WNT) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of WNT gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of WNT genes such as WNT3A and WNT7A.

The present invention relates to a conjugate that includes a nucleic acid ligand bound to a controlled release polymer system, a pharmaceutical composition that contains the conjugate, and methods of treatment using the conjugate. The controlled release polymer system includes an agent such as a therapeutic, diagnostic, prognostic, or prophylactic agent. The nucleic acid ligand that is bound to the controlled release polymer system, binds selectively to a target, such as a cell surface antigen, and thereby delivers the controlled release polymer system to the target.

The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and / or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and / or binding specificity.

This invention relates to compounds, compositions, and methods useful for modulating tumor necrosis factor and / or tumor necrosis factor receptor gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of tumor necrosis factor and / or tumor necrosis factor receptor gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of tumor necrosis factor and / or tumor necrosis factor receptor genes, (TNF and / or TNF receptor).

The invention relates to methods and devices for remote or distributed continuous monitoring of physiologically relevant states. The invention provides for methods to automatically detect deviations or other states in physiological parameters and automatically alert a measured subject, user or other authorized party. The device provides for a universal platform for sensors, and further provides for the automatic compensation or distribution of devices or bioactive agents at appropriate levels and / or intervals in response to deviations or other states sensed in various physiological parameters.

The present invention is directed to a process for amplifying any target nucleic acid sequence contained in a nucleic acid or mixture thereof using a thermostable enzyme. The process comprises treating separate complementary strands of the nucleic acid with a molar excess of two oligonucleotide primers, extending the primers with a thermostable enzyme to form complementary primer extension products which act as templates for synthesizing the desired nucleic acid sequence, and detecting the sequence so amplified. The steps of the reaction can be repeated as often as desired and involve temperature cycling to effect hybridization, promotion of activity of the enzyme, and denaturation of the hybrids formed.

Described are implantable devices and methods for treating various disorders of the pelvic floor by means of electrical stimulation of the pudendal or other nerves, and optional means for delivering drugs in association therewith. A method of precisely positioning and implanting a medical electrical lead so as to provide optimal stimulation of the pudendal nerve or a portion thereof is also described. Placement of a stimulation lead next to or on the pudendal nerve may be performed using conventional prior art techniques through gross anatomical positioning, but usually does not result in truly optimal lead placement. One method of the present invention utilizes neurophysiological monitoring to assess the evoked responses of the pudendal nerve, and thereby provide a method for determining the optimal stimulation site. Additionally, one or more electrical stimulation signals are applied, and optionally one or more drugs are infused, injected or otherwise administered, to appropriate portions of a patient's pelvic floor and pudendal nerve or portions thereof in an amount and manner effective to treat a number of disorders, including, but not limited to, urinary and / or fecal voiding dysfunctions such as constipation, incontinence disorders such as urge frequency and urinary retention disorders, sexual dysfunctions such as orgasmic and erectile dysfunction, pelvic pain, prostatitis, prostatalgia and prostatodynia.

Described are implantable devices and methods for treating various disorders of the pelvic floor by means of electrical stimulation of the pudendal and sacral nerves, or portions thereof, and optional means for delivering drugs in association therewith. Two or more electrical stimulation regimes are applied on a continuous, alternating, intermittent or other basis to the sacral and pudendal nerves, and optionally one or more drugs are infused, injected or otherwise administered, to appropriate portions of a patient's pelvic floor and pudendal nerve and / or sacral nerve, or portions thereof, in an amount and manner effective to treat a number of disorders, including, but not limited to, urinary and / or fecal voiding dysfunctions such as constipation, incontinence disorders such as urge frequency and urinary retention disorders, sexual dysfunctions such as orgasmic and erectile dysfunction, pelvic pain, prostatitis, prostatalgia and prostatodynia.

A system to form and store an electrocardiogram (ECG) signal derived from a cardiac electrical signal that includes an apparatus having a pair of the electrodes to connect to a patient to detect the cardiac electrical signal. A signal sampler samples the cardiac electrical signal to form the ECG signal. A data storage device stores the ECG signal. A computer communicates with the data storage device to retrieve the ECG signal for analysis by software stored in the memory of the computer. The software analyzes a morphology of the amplitude of a plurality of R-wave peaks contained within the ECG signal and / or analyzes a morphology of the area of a plurality of QRS complex pulses contained within the ECG signal.

Methods are disclosed for screening for the occurrence of gene silencing (e.g., post transcriptional gene silencing) in an organism. Also provided are methods for isolating silencing agents so identified.

The invention relates to a liquid phase chip for joint detection of multiple tumor markers and a preparation method thereof. The liquid phase chip comprises micro-balloons of a coupled antibody (at least two of the followings: AFP, CEA, CA125, CA153, CA19-9, CA242, CA72-4, PSA, HGH, Beta-HCG), corresponding biotin-labeled detection antibodies, streptavidin phycoerythrin and vegetable hydrosol or polysaccharide hydrosol which has a solute content of 1-10 wt per thousand and does not contain protein. The preparation of the liquid phase chip comprises refining and purification of hydrosol, coupling between captured antibodies and micro-balloons, preparation of biotin-labeled antibodies, dispersing the coupled micro-balloons into the vegetable hydrosol or the polysaccharide hydrosol, and the like. The liquid phase chip has the advantages of stable performance, good micro-balloon dispersivity, long preservation time, fast and convenient use and operation, small amount of samples in use, high detection sensitivity, wide linear scope and low detection cost, can detect ten tumor markers at most at one time, and requires a cost which is a quarter of the total fee of conventional methods.

An intra-oral dental irradiation device for use in dental procedures for whitening teeth, imaging teeth, and making impressions of tooth structures of a patient. The device features one or a plurality of LED devices mounted to an arched shaped structure which project light upon or through teeth. In the whitening mode the light of the proper spectrum to activate enamel whitening material is projected. In the imaging mode light projected by the LED devices is received by a charged coupled device which communicates the image of the light passing through the teeth from the LED devices, to a computer. In making dental impressions, the device projects light in a spectrum that provides the catalyst to material that hardens when exposed to that spectrum thereby hardening dental impression material when inserted over the teeth of a patient.

This invention relates to compounds, compositions, and methods useful for modulating gene expression using short interfering nucleic acid (siNA) molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of genes, such as expressed pseudogenes associated with the maintenance or development of diseases, disorders, traits, and conditions in a subject or organism. The invention also provides small nucleic acid molecules with reduced or attenuated immunostimulatory properties and methods for designing and synthesizing such small nucleic acid molecules having improved toxicologic properties while retaining RNAi activity.

Various polymers, including cationic polyamine polymers and dendrimeric polymers, are shown to possess anti-proliferative activity, and may therefore be useful for treatment of disorders characterised by undesirable cellular proliferation such as neoplasms and tumours, inflammatory disorders (including autoimmune disorders), psoriasis and atherosclerosis. The polymers may be used alone as active agents, or as delivery vehicles for other therapeutic agents, such as drug molecules or nucleic acids for gene therapy. In such cases, the polymers' own intrinsic anti-tumour activity may complement the activity of the agent to be delivered.

The invention provides, in part, compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also provides, in part, nucleic acid molecules encoding such polypeptides, and methods of making such polypeptides and nucleic acid molecules.

A method of analyzing electrocardiogram (EKG) data for use in the diagnosis of heart disease, prognosis of cardiac conditions, and the monitoring of heart disease therapies is disclosed. The method utilizes a wavelet-based multifractal analysis with one or more of (1) a discrete wavelet smoothing step to remove the effects of abnormal beats; (2) “Levy flight” analysis to detect the frequency of abnormal beats known to adversely affect the multifractal (MF) analysis; and (3) MF alpha analysis, a multifractal extension of monofractal short term (ST) alpha analysis. The invention further comprises an EKG test battery comprising Levy flight anomalous beat / beat cluster screening, followed by (ST) MF alpha analysis and MF Holder analysis (when validated by the Levy flight analysis). The wavelet smoothing step can also be used to classify human EKGs by observing the effect of sequential smoothing on the MF Holder coefficient. Alternative choices to the wavelet smoothing approach to removal of abnormal beat effects include probability distribution function analysis to determine the MF Holder coefficient directly, abnormal beat ridge skeleton removal to remove the offending beats based on a direct multifractal spectrum calculation, and the calculation of various types of entropy coefficients for the EKG time series.

An intra-oral dental irradiation device for use in dental procedures for whitening teeth, imaging teeth, and making impressions of tooth structures of a patient. The device features one or a plurality of LED devices mounted to an arched shaped structure which project light upon or through teeth. In the whitening mode the light of the proper spectrum to activate enamel whitening material is projected. In the imaging mode light projected by the LED devices is received by a charged coupled device which communicates the image of the light passing through the teeth from the LED devices, to a computer. In making dental impressions, the device projects light in a spectrum that provides the catalyst to material that hardens when exposed to that spectrum thereby hardening dental impression material when inserted over the teeth of a patient.

The present invention relates generally to a set of synthetic immunointeractive molecules referred to herein as “demibodies” which are useful in targeting particular cells in a subject. More particularly, the present invention provides a set of demibodies wherein at least two molecules from within the set, each specific for a different antigen on a target cell, are required to interact together at the cell surface in order to form an active complex which directs demibody-mediated cellular or complement mediated cytotoxicity and / or reporter function and / or therapeutic activity. The demibodies of the present invention are useful in the targeting of particular cells such as cancer cells including leukemic cells, pathogens including malarial, bacterial and viral agents, and stem cells including embryonic and adult stem cells and pathogen cells. The present invention provides, therefore, methods of treatment, diagnosis and undertaking research and compositions comprising demibodies useful for same.