Abstract: The present disclosure relates generally to novel lipid nanoparticle (LNP)-based compositions useful for, e.g., the delivery of a site-specific endonuclease or a nucleic acid molecule encoding same, into a target cell. Some embodiments of the disclosure relate to compositions and methods for editing the genome of a cell, which involve contacting the cell with an LNP composition as described herein.

Abstract: Provided is a pharmaceutical composition for the treatment of a disease associated with upregulated periostin expression or periostin splice variant switching, which pharmaceutical composition comprises, as an active ingredient, a nucleic acid capable of inducing skipping of exon 17 in periostin gene transcription and/or a nucleic acid capable of inducing skipping of exon 21 in periostin gene transcription. The pharmaceutical composition of the present invention can treat a disease associated with upregulated periostin expression or periostin splice variant switching, while preventing complete inhibition of the functions of periostin.

Abstract: Embodiments of the disclosure include methods and compositions in which two inter-chromosomal or intra-chromosomal genomic DNA regions are rearranged upon exposure of the genomic DNA to a chimeric RNA that produces fusion of the two regions. The chimeric RNA hybridizes to the two different parts of the genomic DNA and forms a DNA/RNA hybrid in a sequence-specific manner, thereby facilitating genomic rearrangement. In particular embodiments this mechanism is utilized to produce directed gene fusion in targeted genomic DNA regions.

Abstract: The present invention relates to the prevention and/or treatment of retinal dystrophy in a patient, including Leber congenital amaurosis (LCA).

Abstract: The present disclosure provides antisense oligonucleotides targeting Regulator of telomere elongation helicase 1 (RTEL1). The disclosure also provides, enhanced antisense oligonucleotides targeting RTEL1 for use in treating and/or preventing a hepatitis B virus (HBV) infection. Also disclosed are pharmaceutical compositions and their use.

Abstract: The invention relates to iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement factor C3 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of a C3 gene and to treat subjects having a complement component C3-associated disease, e.g., paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), atypical hemolytic uremic syndrome (aHUS), neuromyelitis optica (NMO), multifocal motor neuropathy (MMN), myasthenia gravis (MG), and C3 glomerulonephritis.

Abstract: Disclosed is an oligonucleotide or a pharmacologically acceptable salt thereof, wherein the oligonucleotide comprises at least one defined nucleoside structure, can bind to a human nSR100 gene and has human nSR100 expression inhibiting activity. The oligonucleotide has a length of 12 to 20 mer, and is complementary to a defined target region. Further, disclosed is an nSR100 gene expression inhibitor and a cancer therapeutic agent containing the oligonucleotide or the pharmacologically acceptable salt thereof. The cancer therapeutic agent is used for treatment of small cell lung cancer, prostate cancer, or breast cancer.

Abstract: The present disclosure provides oligonucleotides and double-stranded RNAs (dsRNAs) targeting Hemipteran and Lepidopteran insect pests. Bantam-sequence targets are detailed and shown to be effective targets for RNAi induction utilizing multiple dsRNAs, antisense oligonucleotides, and modified dsRNAs (e.g., 2?-O-methylated and dsRNAs containing non-canonical nucleosides).

Abstract: Systems and method for providing chaperone activity to a protein-containing compound is disclosed. The method includes selecting a nucleic acid based on one or more of the nucleic acid's particular properties and a specific sequence of the nucleic acid and applying the nucleic acid to a compound comprising one or more proteins to provide chaperone activity to the compound.

Abstract: A cancer detection method characterised in that a nematode is bred in the presence of bio-related material originating from a test subject, or a processed product of same, and cancer is detected using the chemotaxis due to the sense of smell of the nematode as an indicator.

Abstract: The invention provides compositions and methods for performing mammalian cell genetics, e.g., genetic screens, using near-haploid cells. The invention further provides genes and gene products isolated using the inventive methods and methods of use thereof.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5? additions to the guide sequence.

Abstract: Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Abstract: Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin ? light chain variable domain.

Abstract: Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin ? light chain variable domain.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity.

Abstract: Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-? chain and a heterologous TCR-? chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.

Abstract: Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Abstract: Provided herein are methods of producing ? cells and precursors thereof utilizing a Wnt signaling inhibitor or PKC activator, or both. Also provided herein are in vitro cultures comprising said cells, methods of treating a subject with a disease characterized by high blood sugar levels over a prolonged period of time by administering said cells, and devices for encapsulating said cells.

Abstract: The present invention provides methods to promote the differentiation of pluripotent stem cells and the products related to or resulting from such methods. In particular, the present invention provides an improved method for the formation of pancreatic hormone expressing cells and pancreatic hormone secreting cells. In addition, the present invention also provides methods to promote the differentiation of pluripotent stem cells without the use of a feeder cell layer and the products related to or resulting from such methods. The present invention also provides methods to promote glucose-stimulated insulin secretion in insulin-producing cells derived from pluripotent stem cells.