Abstract: An engineered type V Cas protein is provided, including a parental type V Cas protein and an HNH domain. The HNH domain is located at an N-terminus of the parental type V Cas protein; or the HNH domain is located between two continuous or non-continuous amino acids of the parental type V Cas protein, named as a first amino acid and a second amino acid, respectively. The first amino acid and the second amino acid are selected from one of amino acids 1 to 10 at the N-terminus of the parental type V Cas protein, and the first amino acid and the second amino acid are different amino acid positions of the parental type V Cas protein; or the first amino acid and the second amino acid are selected from amino acid positions corresponding to amino acids 794 and 795 of SEQ ID NO: 9.

Abstract: The embodiments of the present disclosure relate to one or more compositions or methods that upregulate the production of one or more sequences of micro interfering ribonucleic acid (miRNA). The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule, such as ETS2. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA. Decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions may address the afflictions experienced by the subject due to overexpression of the target biomolecule.

Abstract: The disclosure relates to compositions and methods for altering, e.g., enhancing, the expression of frataxin (FXN), whether in vitro and/or in vivo including, but not limited to, the exploitation of engineered promoters. Such compositions include delivery via administration of an adeno-associated viral (AAV) particle. The compositions and methods of the present disclosure are useful in the treatment of subjects diagnosed with, or suspected of having Friedreich's ataxia or another neuromuscular or neurological condition resulting from a deficiency in the quantity and/or function of frataxin or associated with decreased expression or protein levels of frataxin.

Abstract: The present disclosure is directed to core-shell nanoparticles, compositions comprising core-shell nanoparticles, and methods of their use.

Abstract: The present application provides materials and methods for treating a patient with autosomal dominant RP, both ex vivo and in vivo; materials and methods for editing a RHO gene in a human cell; and materials and methods for editing a P23H mutation in a RHO gene in a human cell. In addition, the present application provides one or more gRNAs or sgRNAs for editing a RHO gene; one or more gRNAs or sgRNAs for editing a P23H mutation in a RHO gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a P23H mutation in a RHO gene. The present application provides a therapeutic for treating a patient with autosomal dominant RP. The present application provides a kit for treating a patient with autosomal dominant RP. In addition, the present application provides a self-inactivating CRISPR-Cas system.

Abstract: Tendon and ligament injuries are common in orthopaedic clinical practice and cause substantial morbidity in sports and in routine daily activities. While surgical reconstruction is effective, the majority of patients suffer from a prolonged period of recovery because of limited regeneration capacity of the tendon-bone interface. Here, the Inventors have established an approach for promoting tendon/ligament integration. By first recruiting endogenous stem cells to the site of injury, bone morphogenic proteins (BMPs), are then delivered in vivo to promote repair. Significant acceleration of healing via the above methods and compositions leads to fast recovery and return to normal activities, thereby providing new therapeutic avenues for treatment of injuries involving the tendon-bone interface.

Abstract: The invention disclosed herein provides methods and materials useful in gene therapy regimens designed to inhibit myelination abnormalities that occur in the urea cycle disorder arginase deficiency. The underlying cause of the progressive neurological dysfunction that occurs in this disorder has been previously unknown and conventional therapies, at best, only slow the onset of neurological dysfunction. This neurological dysfunction results at least in part from the dysmyelination that occurs in the central nervous system due to the lack of adequate hepatic expression of arginase 1. We have discovered an origin of this neurological dysfunction and, using this information, designed materials and associated methods of gene therapy. The methods and materials disclosed herein can inhibit and essentially prevent neurological dysfunction in a murine model of arginase deficiency.

Abstract: The present invention provides mutant adeno-associated virus serotype 5 (AAV5) that exhibit altered capsid properties, e. g., increased infectivity in human liver cells and/or minimal binding to human neutralizing antibodies. The present invention further provides libraries of mutant AAV5 comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV5 and mutant AAV5 libraries, and compositions comprising the mutant AAV5. The present invention further provides recombinant AAV5 (rAAV5) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins.

Abstract: The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules, including cells present in vivo. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described.

Abstract: This invention relates to the expansion of primary cholangiocytes in the form of cholangiocyte organoids (COs) using culture conditions in which canonical Wnt signalling is inhibited and non-canonical Wnt/PCP signalling is potentiated. Methods of expanding primary cholangiocytes, expanded populations of cholangiocytes and medical applications of expanded cholangiocytes are provided.

Abstract: This disclosure provides modified natural killer (NK) cells possessing both NK cell function and dendritic cell function and method of culturing the same. By administration of the modified NK cell, cancer cells in a subject may be effectively inhibited via cell-mediated immunity.

Abstract: Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.

Abstract: Viral vector production processes and methods of purifying a viral vector from a host cell are provided herein.

Abstract: The application describes a contractile cellular biomaterial that is particularly well suited to regenerative therapy of tissue affected by myocardial infraction. The biomaterial comprises a contractile tissue which is contained in an optionally porous solid substrate. The contractile tissue is formed by differentiating stem cells, in particular mesenchymal stem cells. In addition to being contractile, the biomaterial can have inducible paracrine activity. The biomaterial has, in particular, the advantage of not needing to be frozen in order to be conserved.

Abstract: Plasmonics-active nanoprobes are provided for detection of target biomolecules including nucleic acids, proteins, and small molecules. The nucleic acids that can be detected include RNA, DNA, mRNA, microRNA, and small nucleotide polymorphisms (SNPs). The nanoproprobes can be used in vito in sensitive detection methods for diagnosis of diseases and disorders including cancer. Multiplexing can be performed using the nanoprobes such that multiple targets can be detected simultaneously in a single sample. The methods of use of the nanoprobes include detection by a visible color change. The nanoprobes can be used in vivo for treatment of undesireable cells in a subject.

Abstract: The present invention provides a method for producing a heart organoid and/or a lung organoid, comprising the step of: culturing an embryoid body in the presence of an FGF protein on a surface of a gel containing an extracellular matrix constituent protein.

Abstract: A method for preparing chondrocyte pellets including: (a) culturing human induced pluripotent stem cells so as to form and obtain embryoid bodies; (b) inducing the embryonic bodies obtained in step (a) to become outgrowth cells and isolating same; and (c) culturing the outgrowth cells isolated in step (b) in a pellet form. A pharmaceutical composition including the chondrocyte pellets prepared by the preparation method; or a method for preventing or treating arthritis, including administering the chondrocyte pellets prepared by the method to an arthritis patient. Chondrocyte pellets of the present invention have a remarkably high rate of differentiation into chondrocytes, uniform size, and a homogeneous differentiation degree, and a pharmaceutical composition, including the pellets, has excellent cartilage regeneration effects at the site of cartilage damage, and is in injectable form, which does not require surgery, such that pain is relieved and a continuous arthritis treatment is provided.

Abstract: The present disclosure provides a medium and a method for inducing differentiation into functional cerebral cortical cells, wherein the medium comprises a neural medium and a nutritional supplement and the nutritional supplement is selected from a group consisting of SU5402, BIBF1120, IBMX and glucose. The method describes that specific factors such as an inhibitor of FGF signaling pathway, an inhibitor of VEGF signaling pathway and/or an activator of cAMP are added at specific time points during the induced differentiation process to accelerate the differentiation and maturation of the neural cells. Said method can produce stable and healthy neural cells with major functions at about 7 to 14 days after the initiation of the induced differentiation starting from human neural progenitor cells, with reduced manufacturing cost and shortened production time.

Abstract: Nucleic acid molecules include immunoglobulin genes or parts of immunoglobulin genes. The nucleic acid molecules includes the IgM gene (IgHC?) and IgM switch region (S?). The sequences of the S? and the IgHC? are both derived from a transgenic host animal. In this invention, human antibodies are directly generated and no humanization process is required, and the human antibody druggability is increased. The transgenic human antibody mouse has normal early B?cell development, maturation and the B?cell number in comparison with that of wild type animal, thereby facilitating the differentiation of the B?cells. The specificity and diversity of the produced antibody are improved; and the efficiency for screening the therapeutic antibody is improved.

Abstract: The present invention relates to a method for constructing a human pluripotent stem cell-derived liver organoid having enhanced drug metabolic potentials and a liver organoid constructed by the method. Because differentiation is made from human induced pluripotent stem cells dedifferentiated from somatic cells of patients, the cells are easily supplied so that patient-specific liver organoids can be prepared. The organoids can similarly simulate the real human liver structure because they consist of hepatocytes, cholangiocytes, gallbladder cells, and microduct structures, have excellent expression and functions of drug metabolism enzymes, and exhibit drug toxicity, drug metabolic capability, and drug-induced cardiotoxicity. Thus, the organoids can be advantageously used as liver models for searching for pathogenesis of liver diseases and for evaluating drug stability.