62 results about "Cell type specific" patented technology

Described herein are compositions, kits, and methods for potent delivery to a cell of a subject. The cell can be of a particular cell type, such as a basal cell, a ciliated cell, or a secretory cell. In some cases, the cell can be a lung cell of a particular cell type. Also described herein are pharmaceutical compositions comprising a therapeutic or prophylactic agent assembled with a lipid composition. The lipid composition can comprise an ionizable cationic lipid, a phospholipid, and a selective organ targeting lipid. Further described herein are high-potency dosage forms of a therapeutic or prophylactic agent formulated with a lipid composition.

The disclosure relates to growing cells, directing cells to grow into specified cell types, genetically and physically manipulating cells, and addressing one or more individual cells within a mixed cell population. Aspects of the disclosure relate to vectors useful to induce developmental changes in cells, in which those vectors have a temporal component. Vectors of the disclosure encode a controllable, temporal series of events. Once the vectors are delivered into target cells, a series of discrete and different genetic events may be induced. The disclosed methods generally provide for the temporal encoding of multiplex genetic effectors in vector format for cell state transitions.

Provided herein are viral particles comprising a heterologous viral glycoprotein and a targeting moiety wherein the targeting moiety comprises a polypeptide comprising the formula T-S1 wherein T is a target binding domain and Si is a stem moiety. The stem portion may comprise a variant Fc domain. The stem portion may comprise a flexible polypeptide domain. The targeting moiety comprising the formula T-S1 may be incorporated into viral particles to help target such particles to specific cell types. Also provided herein are compositions comprising the viral particles, and methods of use thereof.

A method for identifying key targets or biomarkers of a disease at a cell specific level according to a two-step process that comprises: (1) identifying cell type-specific candidate targets / biomarkers with genetically defined causal relationships to one or more disease features by performing causal analysis (e.g., 2 sample mendelian randomization); and (2) ranking candidate targets / biomarkers by analyzing the interconnectivity between the identified candidate targets / biomarkers and common interactors / regulators in a customized cell type-specific knowledge graph.

It is an object of the present invention to provide transport microcapsules that are ingested by a target cell type and permanently or temporarily alter the target cell without thereby causing a toxic effect on the cell. The solution according to the invention consists in the use of a monodisperse core to thereby produce polyelectrolyte nanocapsules having cell-specific dimensions, in which the dimensions for hematopoietic cells range from 20 to 80 nm, preferably from 40 to 60 nm. The size of the particles must be in a very narrow range to prevent the occurrence of toxic effects. In order to maintain the low toxicity of nanomicrocapsules, it is also important to remove nanoparticles (cores) surrounding which create microcapsules prior to use. The method for this purpose is known in the prior art (e.g., using EDTA removal). Another object of the invention is the stabilization of transport microcapsules. The solution according to the invention consists in modifying microcapsules, layers and / or carriers to be packaged by functional groups, allowing stabilization and thus long-term storage at room temperature. The third purpose of the invention is targeted introduction of transport microcapsules. The solution according to the invention is functionalization of the layer by chemical modification and / or supplementation of the layer with antibodies, proteins or peptides.

The subject matter described here relates to an enhancer specific to a subset of cholinergic neurons, that can control gene expression in a highly neuron-specific manner, wherein the enhancer is compatible with AAVs packaging and can induce gene expression or knockdown in cholinergic neurons in both post-natal and adult subjects.

The present invention provides targeting polyplexes comprised of (i) nucleic acids, in particular nucleic acids encoding pharmaceutically active peptides or proteins, and (ii) targeting conjugates comprising LPEI and PEG fragments that are connected by discrete linkages formed through defined, chemoselective reactions. Thus, the LPEI fragment is bonded in a linear end- to-end fashion to a single PEG fragment. The linear conjugates are further conjugated to a targeting fragment to enable selective interaction with a particular cell type. The polyplexes selectively deliver the nucleic acids to the targeted cells resulting in high expression and efficient protein translation as well as secretion of the encoded pharmaceutically active proteins.

Provided is a viral vector having a lipid bilayer envelope, the lipid bilayer envelope comprising an antibody binding domain displayed outside the envelope, the antibody binding domain being cell type specific; a viral envelope protein exhibited outside the envelope, the viral envelope protein being capable of promoting infection of the same cell type; and a nucleic acid molecule comprising a promoter capable of being expressed in the same cell type. Methods of making the viral vectors and methods of modifying cells and treating diseases / conditions using the viral vectors are also provided.

To provide compositions and methods for delivering therapeutic antibodies to a specific cell type and to specific locations within that cell.SOLUTION: Disclosed are compositions comprising an antibody conjugated to one or more molecular guidance system (MGS) peptides. Disclosed are methods of treating a subject in need thereof comprising administering to the subject in need thereof an effective amount of an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target involved in the disease process. Disclosed are methods of targeting an intracellular target, comprising administering an antibody conjugated to one or more MGS peptides, wherein the antibody targets an intracellular target.SELECTED DRAWING: None

A method for using a device for manipulating and / or determining one or more characteristics of cells or micro-bead contained within a biological sample is provided. The device comprises: a sorting component configured to separate cell-containing or micro-bead containing microdroplets from empty ones into a population of cell-containing or micro-bead containing first microdroplets; a microdroplet manipulation component configured to manipulate the first microdroplets in a first zone configured to arrange the first microdroplets into an array for optical inspection and a second zone located within or adjacent the first zone and configured to detect merged microdroplets in one or more detection windows; and an optical detection system configured to detect an optical signal from the microdroplets via the one or more detection windows and to analyse the contents of each microdroplet to determine one or more characteristics of a cell or micro-bead contained in that microdroplet. The method comprises the steps of: creating from the biological sample aqueous first microdroplets in an immiscible carrier fluid, at least some of which are believed to contain cells of a particular cell type; moving the first microdroplets along a pathway using real or virtual electrodes to at least one microdroplet-merging location; merging reporter system containing microdroplets into the first microdroplets to produce merged microdroplets; analyzing the contents of each merged microdroplet with an optical detection system and detecting an optical signal characteristic of an interaction between the cell or micro-bead and the reporter system.

The invention discloses a method for constructing a neurodevelopmental disorder animal model based on central nervous system myelin sheath function change and application, and belongs to the technical field of biological engineering. An Msl2 gene conditional knockout mouse model is constructed by adopting a gene engineering technology, the space-time specific knockout of a second exon of the Msl2 gene in a specific cell type is realized through a Cre-LoxP recombinase system, and the exon encodes a key enzyme activity region for catalyzing ubiquitination. Model construction is based on central nervous system oligodendrocyte / myelin sheath dysfunction, the behavior phenotype of the model is similar to the behavior of a typical neurodevelopment disorder animal, a brand new perspective is provided for exploring an etiology mechanism, model mice can be prepared on a large scale by performing directional mating on the gene modified mice, and the development of the model is promoted. And consistency of different experiment batches and reliable reproduction of experiment data are ensured.

A protein nanospheres and method to treat dysfunction from chemotherapy and immunosuppressive therapy, and a manufacture of fibrinogen-coated albumin spheres (FAS) and High-Fibrinogen Spheres (HFS) which have higher concentrations of fibrinogen molecules per sphere than FAS, and their use for medical treatments. Both kinds of nanoparticles are effective in the mitigation of the toxic effects of certain chemotherapeutic and radiological agents that are typically used in the treatment of cancer, or the treatment of autoimmune diseases, or for patients with both diseases. FAS and HFS can exert their beneficial effects via a variety of mechanisms which match the need of the body for specific cell types, including any of the subgroups of T cells and antibody producing cells, the relative concentration of each kind is vital to the balance between tumor surveillance and autoimmune disease suppression.

The present invention relates to polyplexes comprising linear conjugates of LPEI and PEG. The LPEI and PEG fragments of the linear conjugates are preferably linked by a [3+2]cycloaddition between an azide and an alkene or an alkyne to produce a 1, 2, 3 triazole or a 4,5-dihydro-1H-[1,2,3]triazole. The linear conjugates are further conjugated to a targeting fragment capable of binding to prostate specific membrane antigen (PSMA) to enable selective interaction with a particular cell type. The conjugates can form polyplexes with therapeutic agents such as nucleic acids to deliver the therapeutic agents to cells.

To provide radiolabeled biomolecules and methods for radiolabeling biomolecules with radioactive halogen atoms, where the methods minimize loss of the radioactive halogen due to dehalogenation in vivo, preserve the biological activity of the biomolecules, maximize retention of radioactivity in cancer cells, and minimize retention of radioactivity in normal tissues after in vivo administration.SOLUTION: Some of such radiolabeled biomolecules comprise a radioactive metal atom in place of or in addition to the radioactive halogen. The biomolecules have affinity for particular types of cells and may specifically bind to certain cells, such as cancer cells. Relevant biomolecules include antibodies, monoclonal antibodies, antibody fragments, peptides, other proteins, nanoparticles and aptamers.SELECTED DRAWING: None

The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.

Various embodiments are directed to the analysis of fragmentation patterns of cell-free DNA (cfDNA) circulating in cerebrospinal fluid (CSF) and the potential applications. CSF is an important liquid biopsy sample used to study the central nervous system and related disorders, such as infection and malignancies. The characterization of fragmentation patterns of cfDNA in CSF includes the size profile, end motif, cleavage profiles, and the determination of epigenetic features, including methylation. Various applications can use one or more properties of fragmentation pattern, for example, in the determination of the proportional contribution of a particular cell types in the CSF cfDNA pool. Another purpose is the diagnosis of pathology in the central nervous system, by the detection of clinically relevant DNA (e.g., tumor fraction, pathogen). DNA fragments in CSF can be analyzed in various ways, including using short-read sequencing, and / or long-read sequencer technologies.

Provided are isolated, cloned enhancer element sequences that target certain neuronal cell types, subtypes, and / or populations in the brain and CNS. The isolated and cloned enhancer elements can target a gene of interest, such as a therapeutic gene or an effector gene, to be expressed in the certain cell types. Virus vectors containing the isolated, cloned enhancer element sequences, particularly, recombinant adeno-associated virus (rAAV) vectors, and a gene or polynucleotide to be expressed in a given neuronal cell type are described. The rAAV vectors, compositions and methods are useful for treating subjects afflicted with neuropsychiatric and neuropathological diseases, disorders and conditions and symptoms thereof.

The present disclosure is directed to scaffold materials patterned with cell adhesion targets that permit the attachment and growth of predetermined cell types onto the scaffold. By selecting specific ligands that are patterned on the scaffold, particular cell types, including those engineered for this specific purpose, will attach and proliferate to create designed tissues and organs.

The present invention relates to polymer complexes comprising linear conjugates of LPEI and PEG. The LPEI fragment and the PEG fragment of the linear conjugate are preferably connected through [3 + 2] cycloaddition reaction between azide and olefin or alkyne to generate 1, 2, 3 triazole or 4, 5-dihydro-1H-[1, 2, 3] triazole. The linear conjugates are preferably further conjugated to targeting fragments to achieve selective interaction with specific cell types. The conjugate may form a polymer complex with a therapeutic agent (e.g., a nucleic acid) to deliver the therapeutic agent to a cell.

The present invention relates to a polyplex comprising a linear conjugate of LPEI and PEG. The LPEI and PEG fragments of the linear conjugate are preferably linked by a [3+2] cycloaddition between azide and alkene or alkyne to generate 1,2,3 triazole or 4,5-dihydro-1H-[1,2,3]triazole. The linear conjugate is further conjugated to a targeting fragment that can bind to prostate-specific membrane antigen (PSMA) to enable selective interaction with specific cell types. The conjugate can form a polyplex with a therapeutic agent, such as a nucleic acid, to deliver the therapeutic agent to cells.

The disclosure relates to growing cells, directing cells to grow into specified cell types, genetically and physically manipulating cells, and addressing one or more individual cells within a mixed cell population. Aspects of the disclosure relate to vectors useful to induce developmental changes in cells, in which those vectors have a temporal component. Vectors of the disclosure encode a controllable, temporal series of events. Once the vectors are delivered into target cells, a series of discrete and different genetic events may be induced. The disclosed methods generally provide for the temporal encoding of multiplex genetic effectors in vector format for cell state transitions.

The present invention provides a targeting polyplex composed of (i) a nucleic acid, particularly a nucleic acid encoding a pharmaceutically active peptide or protein, and (ii) a targeting conjugate comprising an LPEI and a PEG fragment connected by distinct linkages formed by a defined chemoselective reaction. Thus, the LPEI fragment is linked to a single PEG fragment in a linear, end-to-end manner. The linear conjugate is further conjugated to a targeting fragment to enable selective interaction with specific cell types. The polyplex selectively delivers the nucleic acid to target cells, resulting in high expression and efficient protein translation and secretion of the encoded pharmaceutically active protein.

The present invention provides targeted polymer complexes comprising: (i) a nucleic acid, in particular a nucleic acid encoding a peptide or protein having pharmaceutical activity; and (ii) a targeting conjugate comprising LPEI and PEG fragments linked by discrete bonds formed by a defined chemically selective reaction. Thus, the LPEI fragment is bonded to a single PEG fragment in a linear end-to-end manner. The linear conjugate is further conjugated to a targeting fragment to achieve selective interaction with a particular cell type. The polymer complexes selectively deliver nucleic acids to target cells, thereby achieving high expression and efficient protein translation and secretion of the encoded pharmaceutically active proteins.

The invention relates to a method of differentiating immature cells to a specific cell lineage of interest and / or to a specific cell type, said method comprising: i) Silicificating cells of said specific cell lineage to obtain silicified cells; ii) Calcinating a plurality of the silicified cells to obtain a scaffold; iii) Contacting the scaffold with the immature cells; iv) Culturing the immature cells in contact with the scaffold in a culture medium, thereby inducing differentiation of the immature cells into differentiated cells of said specific cell lineage and / or of said specific cell type. The invention also relates to scaffolds, silicified cells and kits for the differentiation of cells.

The present invention provides a polycistronic reporter vector, a receptor stem cell for accepting the polycistronic reporter vector, and a multi-reporter cell for use in an assay for spectroscopic analysis of two or more polypeptides in a living cell, wherein the vector comprises a reporter polypeptide under the control of a lineage-specific promoter to act as a barcode for a particular cell type. Methods of making a polycistron reporter vector, recipient cells for accepting a polycistron reporter vector, and a multi-reporter cell are provided. Libraries and kits comprising a polycistron reporter vector, recipient cells for accepting the polycistron reporter vector, and multi-reporter cells are provided. Methods of spectrally analyzing / determining the multi-reporter cells and the multi-reporter cell banks are provided.

The application relates to a retinal cell type-based visual function related parameter acquisition system and belongs to the technical field of medical auxiliary systems. The application aims to accurately acquire a retinal cell type-based visual function related parameter acquisition system of L cone, M cone, S cone, ipRGCs and other different retinal cell type function related physiological parameters. The system of the application comprises a stimulation presentation module, a brightness calibration module, a biological signal acquisition module, a multi-dimensional parameter extraction and cell type specific parameter decoupling module, a parameter analysis and standardized output module, a user interaction module and a data storage module. The application can provide a portable, objective, non-invasive and cell type specific retinal function related parameter acquisition technology, provide comprehensive and reliable technical support for visual function evaluation, is suitable for large-scale parameter acquisition and home monitoring, and solves many limitations of the prior art.

The inventors developed a new system to modify tropism of syncytins, envelope proteins, which can be used to functionalize particles such as virus particle or more particularly viral-like particles (VLPs), and used for gene transfer or other applications. In particular, they created a fusion protein containing the Syncytin-1 (SYN) signal sequence (SS), a targeting moiety (either natural or engineered), the SYN protein and a flexible linker between SYN and the targeting moiety to enhance transduction of the cell type expressing the receptor or the antigen targeted by the targeting moiety, for instance hematopoietic stem progenitor cells (HSPCs). The inventors demonstrated that the fusion strategy allows modification of syncytin tropism towards different receptors in order to target f the desired cell type. The system is adaptable to other desired antigens to retarget the fusion protein to a specific cell type.

Described herein are compositions and methods for potent and long-lasting gene editing in a cell. The gene editing may result in an increase in function of a gene product. The cell can be of a particular cell type, such as a basal cell, a ciliated cell, or a secretory cell. In some cases, the cell can be a lung cell of a particular cell type. The presently disclosed compositions comprise a lipid composition, which can comprise an ionizable cationic lipid, a sterol, a phospholipid, and a selective organ targeting lipid. Also described herein are methods for treating a disease or disorder, such as a lung disease or disorder, involving the presently disclosed compositions.

The invention relates to a method for predicting the metabolic condition of a cell culture of cells of a specific cell type. The method comprises providing (102) a metabolic model (402) of a cell of the specific cell type and carrying out the following steps at each of a plurality of points in time during the cultivation of the cell culture: receiving (106) measured concentrations of several extracellular metabolites and a measured cell density in the culture medium; inputting (108) the received measured values as input parameter values into a trained machine learning program logic—MLP (218); predicting (110) extracellular flows (408) of the extracellular metabolites at a future point in time by means of the MLP; carrying out (112) a metabolic flow analysis for calculating the intracellular flows at the future point in time on the basis of the predicted extracellular flows and the stoichiometric equations of the metabolic model.

To provide a method of differentiating a pluripotent stem cell of mammalian origin into a desired cell type by predicting the direction of cell differentiation caused by induction of expression of a transcription factor.SOLUTION: The present invention provides a method for differentiating a pluripotent stem cell into a transformed cell, comprising introducing a transcription factor into a pluripotent stem cell of mammalian origin, wherein the transcription factor has a z-value of 3 or more for a specific cell type in the table of a human gene expression correlation matrix.SELECTED DRAWING: None