Abstract: The invention relates to C. acnes carrying DNA vectors with a C. acnes phage packaging signal and a gene of interest. The invention encompasses a C. acnes producer cell carrying DNA vectors, with a C. acnes phage packaging signal and a gene of interest, for the production of phage-derived particles that can robustly transduce C. acnes receiver cell allowing transgene expression. The invention encompasses C. acnes phage-derived particles carrying these vectors, C. acnes containing these vectors or modified by transduction of these phage-derived particles, and methods of using these phage-derived particles.

Abstract: A targeted DNA demethylation method (Mini-CRISD) and a fusion protein used in the method are provided. The Mini-CRISD method can targets delivery of demethylation activity through engineered miniature dCjCas9 to deliver engineered miniature ROS1 demethylation effector to specific DNA sequences and/or specific genomic locations (such as CpG islands) to achieve targeted demethylation of specific DNA.

Abstract: The present invention relates to systems and methods for screening compounds and/or mutant ribosomal proteins in a eukaryotic cell that increase or decrease the translation of a target gene and thereby ameliorate or revert a defective and/or undesired translation of a target gene. Disclosed are compounds and proteins as identified with the methods and systems of the invention, pharmaceutical and cosmetic compositions thereof, their uses for the preparation of a medicament, methods of treatment of a disease or condition or cosmetic condition related to the defective translation of a gene, for example genetic diseases such as Epidermolysis bullosa, as well as diagnostic measures practical for the clinical evaluation of such diseases or conditions. Also, kits are provided which comprise the identified compounds and/or proteins in addition to suitable means for performing the methods of the invention.

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: Provided herein are genetically engineered cells containing one or more modulated metabolic genes, where the expression of the modulated metabolic gene(s) can be greater than that of an unmodified control. Also provided herein are methods of making the genetically engineered cells using synergistic activation mediator CRISPR-Cas9. Further provided herein are high throughput assays that can employ the genetically engineered cells provided herein.

Abstract: The present invention enables simultaneous and stable expression of a plurality of foreign genes by using a stealthy RNA gene expression system that is a complex that does not activate the innate immune mechanism and is formed from an RNA-dependent RNA polymerase, a single-strand RNA binding protein, and negative-sense single-strand RNAs including the following (1) to (8): (1) a target RNA sequence that codes for any protein or functional RNA; (2) an RNA sequence forming a noncoding region and derived from mRNA expressed in animal cells; (3) a transcription initiation signal sequence recognized by the RNA-dependent RNA polymerase; (4) a transcription termination signal sequence recognized by the polymerase; (5) an RNA sequence containing a replication origin recognized by the polymerase; (6) an RNA sequence that codes for the polymerase and of which codons are optimized for the species from which an introduction target cell is derived; (7) an RNA sequence that codes for a protein for regulating the activity o

Abstract: Methods and compositions are provided herein for assessing CRISPR/Cas-mediated non-homologous end joining (NHEJ) activity and/or CRISPR/Cas-induced recombination of a target genomic locus with an exogenous donor nucleic acid in vivo and ex vivo. The methods and compositions employ cells and non-human animals comprising a Cas expression cassette such as a genomically integrated Cas expression cassette so that the Cas protein can be constitutively available or available in a tissue-specific or temporal-specific manner. Methods and compositions are also provided for making and using these non-human animals, including use of these non-human animals to assess CRISPR/Cas activity in vivo via adeno-associated virus (AAV)-mediated delivery of guide RNAs to the non-human animals.

Abstract: The field of the invention encompasses synthetic chromosome compositions and methods that allow single cell spatiotemporal analysis in response to differentiation cues and labeling of transplanted cells to monitor the fate and function of such cells in the patient recipient.

Abstract: The present invention enables simultaneous and stable expression of a plurality of foreign genes by using a stealthy RNA gene expression system that is a complex that does not activate the innate immune mechanism and is formed from an RNA-dependent RNA polymerase, a single-strand RNA binding protein, and negative-sense single-strand RNAs including the following (1) to (8): (1) a target RNA sequence that codes for any protein or functional RNA; (2) an RNA sequence forming a noncoding region and derived from mRNA expressed in animal cells; (3) a transcription initiation signal sequence recognized by the RNA-dependent RNA polymerase; (4) a transcription termination signal sequence recognized by the polymerase; (5) an RNA sequence containing a replication origin recognized by the polymerase; (6) an RNA sequence that codes for the polymerase and of which codons are optimized for the species from which an introduction target cell is derived; (7) an RNA sequence that codes for a protein for regulating the activity o

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

Abstract: The invention relates to C. acnes carrying DNA vectors with a C. acnes phage packaging signal and a gene of interest. The invention encompasses a C. acnes producer cell carrying DNA vectors, with a C. acnes phage packaging signal and a gene of interest, for the production of phage-derived particles that can robustly transduce C. acnes receiver cell allowing transgene expression. The invention encompasses C. acnes phage-derived particles carrying these vectors, C. acnes containing these vectors or modified by transduction of these phage-derived particles, and methods of using these phage-derived particles.

Abstract: Disclosed herein are therapeutic agents capable of increasing the expression level of ELOVL2. Also described herein are therapeutic agents that reduce or slow an aging phenotype. Methods for treating age-related eye diseases or conditions are also provided. Methods for treating an age-related eye disease or condition in a subject by administering one or more therapeutic agents are provided.

Abstract: Expression-enhancing nucleotide sequences for eukaryotic expressions systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Genomic integration sites providing enhanced expression and methods of use thereof are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.

Abstract: The present invention is directed to methods and materials for RNA-mediated gene assembly from oligonucleotide sequences. In some embodiments, the oligonucleotides used for gene assembly are provided in an array format. An RNA polymerase promoter is appended to surface-bound oligonucleotides and a plurality of RNA copies of each oligonucleotide are then produced with an RNA polymerase. These RNA molecules self-assemble into a desired full-length RNA transcript by hybridization and ligation. The resulting RNA transcript may then be converted into double stand DNA useful in a variety of applications including protein expression.

Abstract: The various embodiments of the disclosure relate generally to processes, methods, and systems for generating functional B cells ex vivo. It is particularly useful for ex vivo generation of antigen-specific germinal-center (GC) like B cells that are capable of efficient B cell expansion, immunoglobulin (Ig) class switching/class switching recombination (CSR), expression of germinal B cell phenotypes, antibody secretion, and somatic hypermutation (SHM) and resulting affinity maturation center phenotypes.

Abstract: Provided herein are compositions and methods for assembling nucleic acid sequences encoding T-cell receptors.

Abstract: Two or more conditional, dominant, lethal gene expression systems provide high levels of penetrance in insects. Lethality is induced at an earlier stage of development and the risk of biochemical resistance is reduced, as compared to a single insect conditional, dominant, lethal gene expression system. The invention is useful for the control of insect populations.

Abstract: Therapeutic uses P2X7 inhibition and inhibition of IRAK1 and/or IRAK4, methods protecting a cell, and screening methods for identifying inhibitors are described herein.

Abstract: In one aspect, disclosed herein is a method for evaluating the immunogenicity of a test substance in a short period of time by using, as an indicator of the immunogenicity of the test substance, the proportion of IL-2-secreting cells in a T cell population (preferably a CD4+ T cell population) at a time point during the early stage of IL-2 secretion after stimulation of the T cell population with the test substance (preferably 24 hours to 72 hours after the stimulation with the test substance).