The present invention provides a conjugate of an oligonucleotide having a nucleic acid sequence expected to have a pharmacological effect in hepatic parenchymal cells with a biantennary GalNAc unit, or a pharmaceutically acceptable salt thereof, and a medicament or the like containing the same as an active component.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL10R and/or a human or chimeric (e.g., humanized) IL10, and methods of use thereof.

The object of the present invention is to provide a polynucleotide which can be inserted into an expression vector and can enhance the transcriptional activity of a predetermined promoter under heart failure.

The object is achieved by an enhancer polynucleotide comprising a polynucleotide consisting of a sequence having 80% or more identity with a sequence represented by SEQ ID NO: 1, or a polynucleotide consisting of a sequence having 80% or more identity with a sequence represented by SEQ ID NO: 2, wherein the enhancer polynucleotide responds to heart failure (where the enhancer polynucleotide excludes a polynucleotide having the same sequence as a sequence represented by SEQ ID NO: 13 and a polynucleotide having the same sequence as a sequence represented by SEQ ID NO: 12).

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions including apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do not reduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm including administration of a composition including apoptotic cells or an apoptotic cell supernatant.

Described herein are methods of prolonging or reactivating organogenesis in a subject in need thereof (e.g., a subject that has impaired organ function such as a prematurely born infant). The methods comprise increasing the expression or activity of Lin28A or Lin28B proteins, inhibiting the expression or activity of let-7 family microRNAs, and/or inhibiting the expression or activity of Dis3L2 exonuclease.

Disclosed herein are antigenic peptide-MHC complexes, termed comPACT polypeptides and comPACT polynucleotides, and methods of producing such complexes. Also discloses herein are methods of producing libraries of comPACT polynucleotides and polypeptides, and their exemplary use in capturing cancer neoepitope-reactive T cells with high accuracy. Dual particle detection approaches for detection of neoantigen specific T cells with improved sensitivity and specificity are provided. Signal to noise ratio analysis of isolated T cells for detection of neoantigen-specific T cells with improved T cells is also provided.

The purpose of the present invention is to provide a novel medical application of pluripotent stem cells (muse cells) in regeneration medicine. The present invention provides a cell preparation and a pharmaceutical composition which are for amelioration and treatment of brain disorders resulting from fetal growth retardation, such as abnormal motor quality or abnormal neurological development, and which contain SSEA-3 positive pluripotent stem cells isolated from a mesenchymal tissue from a live body or cultured mesenchymal cells. It is assumed that this cell preparation is based on a mechanism where muse cells that are administered to objects having the disorders are engrafted on an impaired brain tissue, thereby ameliorating or treating the disorders.

The present invention concerns an expression system for systemic administration comprising a sequence encoding a FKRP protein, and: —a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and a target sequence of an miRNA expressed in the heart; or—a promoter sequence allowing the expression at a therapeutically acceptable level of FKRP in the skeletal muscles and presenting a promoter activity at a toxically acceptable level in the heart; and its use for the treatment of various diseases linked to FKRP deficiencies.

Transgenic mammals that express bovine-based immunoglobulins are described herein, including transgenic rodents that express bovine-based immunoglobulins for the development of bovine therapeutic antibodies.

Provided herein are polynucleotide constructs comprising a CD11b promoter operably linked to a nucleic acid encoding one or more therapeutic polypeptides, to vectors, cells, and/or compositions comprising the same, and to methods of their use.