Abstract: Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldenström macroglobulinemia.

Abstract: Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldenström macroglobulinemia.

Abstract: Aspects of the disclosure relate to methods and synthetic regulatory systems for more efficient nuclease-mediated homology-directed repair (HDR). In particular, provided herein are methods for more efficient in vivo and in vitro HDR-based gene editing where the methods comprise introducing into a cell a synthetic regulatory system comprising Cas nuclease, guide RNAs (gRNAs) having various lengths and configured to target distinct nucleotide sequences for simultaneous transcriptional repression (or activation) and genome editing via double stranded break and use of a donor nucleic acid molecule as a template for repair.

Abstract: Aspects of the disclosure relate to synthetic regulatory systems composed of a multifunctional Cas nuclease, at least two guide RNAs (gRNAs) configured to target distinct nucleotide sequences, and a multilayered regulatory control element comprising ribozyme-based safety switches providing spatial and temporal control over the synthetic circuit in vivo.

Abstract: Disclosed are effective, specific, and durable pain management therapies using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-based) epigenetic modulation of endogenous pathways involved in pain.

Abstract: The present disclosure relates to methods for expanding populations of hematopoietic stem cells (HSCs) using a genetically engineered human fetal liver niche and compositions of purified ex vivo expanded HSCs. Also provided herein are methods of using such expanded HSC cell populations for clinical applications including allogeneic hematopoietic stem cell transplantation and for drug discovery and modeling human liver development.

Abstract: Provided herein are methods and compositions for reducing an undesirable T cell immune response in human patients prior to and/or during gene therapy using CRISPR/Cas9-based genetic modulation.

Abstract: Provided herein are methods and compositions for reducing an undesirable T cell immune response in human patients prior to and/or during gene therapy using CRISPR/Cas9-based genetic modulation.

Abstract: Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldanstrom macroglobulinemia.

Abstract: The present disclosure relates to synthetic liver organoids and methods of using such synthetic liver organoids for various applications including drug discovery and modeling human liver development. In particular, provided herein are methods of producing and using synthetic mature liver organoids comprising mature, functional cells found in the human liver.

Abstract: Provided herein are tools for understanding and engineering dynamics of synthetic genetic circuits which utilize CRISPR components. More particularly, methods, systems, and compositions for directing Cas9 activity using a fluorescent guide RNA (fgR-NA) which fluoresces in the presence of small molecules (e.g., DFHBI-IT) are described and illustrated in the present provisional application.

Abstract: Aspects of the disclosure relate to synthetic regulatory systems composed of a multifunctional Cas nuclease, at least two guide RNAs (gRNAs) configured to target distinct nucleotide sequences, and a multilayered regulatory control element comprising ribozyme-based safety switches providing spatial and temporal control over the synthetic circuit in vivo.

Abstract: Aspects of the disclosure relate to synthetic regulatory systems comprising a multifunctional Cas nuclease and at least two guide RNAs (gRNAs) including a truncated gRNA and an multilayered regulatory control element. The synthetic regulatory system modulates endogenous gene expression, including transcriptional repression and transcriptional activation of one or more endogenous genes of a mammalian inner ear cell with multiple safety switches. Also provided herein are methods for modulating hearing sensitivity in damaged cells of the organ of corti.

Abstract: Provided herein are methods and compositions for reducing an undesirable T cell immune response in human patients prior to and/or during gene therapy using CRISPR/Cas9-based genetic modulation.

Abstract: Provided herein are tools for understanding and engineering dynamics of synthetic genetic circuits which utilize CRISPR components. More particularly, methods, systems, and compositions for directing Cas9 activity using a fluorescent guide RNA (fgR-NA) which fluoresces in the presence of small molecules (e.g., DFHBI-IT) are described and illustrated in the present provisional application.

Abstract: Aspects of the disclosure relate to methods and synthetic regulatory systems for more efficient nuclease-mediated homology-directed repair (HDR). In particular, provided herein are methods for more efficient in vivo and in vitro HDR-based gene editing where the methods comprise introducing into a cell a synthetic regulatory system comprising Cas nuclease, guide RNAs (gRNAs) having various lengths and configured to target distinct nucleotide sequences for simultaneous transcriptional repression (or activation) and genome editing via double stranded break and use of a donor nucleic acid molecule as a template for repair.

Abstract: Aspects of the disclosure relate to synthetic regulatory systems composed of a multifunctional clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) nuclease and at least two distinct guide RNAs (gRNAs). The synthetic regulatory system modulates cleavage and transcription, including repression and activation, in a mammalian cell such as a human cell.

Abstract: Provided herein, in some embodiments, are modular transcriptional architectures and methods for regulated expression of guide RNAs in cells, such as human cells, which are based on Clustered Regularly Interspaced Palindromic Repeats (CRISPR) systems.