C12N15/635

DEAMINASE-BASED RNA SENSORS

RNA editing tools for use in systems designed to measure RNA in vivo and manipulate specific cell types are disclosed herein. An RNA sensor system comprising a) a single-stranded RNA (ssRNA) sensor comprising a stop codon and a payload; optionally wherein the ssRNA sensor further comprises a normalizing gene; and b) an adenosine deaminase acting on RNA (ADAR) deaminase; wherein the sensor is capable of binding to a ssRNA target to form a double-stranded RNA (dsRNA) duplex that becomes a substrate for the ADAR deaminase; wherein the substrate comprises a mispairing within the stop codon; and wherein the mispairing is editable by the ADAR deaminase, which editing can effectively remove the stop codon so as to enable translation and expression of the payload. A method of quantifying ribonucleic acid (RNA) levels using the RNA sensor system is also disclosed.

BACTERIAL BIOSENSOR SYSTEM
20230063616 · 2023-03-02 ·

The disclosure relates to a biosensor on the bacterial cell surface for sensing and responding to extracellular molecules. Related methods of using the bacterial cells to inducibly express a protein of interest and/or a bioactive RNA molecule in a subject are disclosed. Related methods of using the bacterial cells to inducibly express a protein of interest or to detect a target of interest in a sample are also disclosed.

REGULATED SYNTHETIC GENE EXPRESSION SYSTEMS

The technology described herein is directed to regulated synthetic gene expression systems. In one aspect described herein are synthetic transcription factors (synTFs) comprising a DNA binding domain, a transcriptional effector domain, and a regulator protein. In other aspects described herein are gene expression systems comprising said synTFs and methods of treating diseases and disorders using said synTFs.

METHODS FOR ROBUST DESIGN OF MODULAR REPRESSORS
20230064064 · 2023-03-02 ·

A method can include receiving a protein sequence (S) of a hybrid repressor, determining an original compatibility score C(S), where the compatibility score C is a function of the protein sequence (S) and predicting, based on the compatibility score C, a performance of the hybrid repressor. The hybrid protein sequence includes a plurality of DNA-binding modules (DBMs) and a plurality of ligand-binding modules (LBMs).

ACTIVATION OF LYTIC GENES IN CANCER CELLS

The present disclosure provides methods of inducing EBV early lytic cycle genes with high specificity. These methods slow or stop cancer cell growth in vitro and in vivo.

MONOCLONAL ANTIBODY
20230112794 · 2023-04-13 ·

The present invention discloses an monoclonal antibody, which can bind to HyIL-6 with the binding constant 2.86×10.sup.−10 and significantly inhibit IL-6/IL-6R/gp130 complex formation. In addition, the monoclonal antibody of the present invention effectively inhibits HyIL-6-stimulated signal transducer and activator of transcription 3(STAT3) activation and related vascular endothelial growth factor (VEGF) induction. Data from hydrogen deuterium exchange mass spectrometry (HDX-MS) demonstrate that the antibody of the present invention mainly binds to site IIIa of IL-6 and blocks the final step in the interaction between gp130 and IL-6/IL-6R complex. Additionally, data from ELISA binding assays and kinetics assays indicate that the antibody of the present invention interacts simultaneously with IL-6 and IL-6R, while it does not interact with IL-6R alone. The unique features of the antibody of the present invention offer a novel alternative for IL-6 blockade and illuminate a better therapeutic intervention targeting IL-6.

NUCLEASE-MEDIATED MODULATION OF GENE EXPRESSION

The present disclosure relates to methods, compositions, and automated multi-module cell processing instruments for modulation of gene utilizing nuclease-mediated systems, and in particular, inactive (“dead”) nuclease-mediated CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) systems.

NUCLEIC ACID SEQUENCE FOR REGULATION OF TRANSGENE EXPRESSION

The present invention relates to the field of gene therapy. In particular, the invention relates to a nucleic acid molecule comprising a nucleic acid sequence able to regulate the expression of a transgene of interest, to a vector or a cell comprising said nucleic acid molecule, and uses thereof.

RECOMBINANT BACTERIA ENGINEERED TO TREAT DISEASES ASSOCIATED WITH URIC ACID AND METHODS OF USE THEREOF

The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells that comprise a uric acid catabolism enzyme, e.g., a uric acid degrading enzyme, for the treatment of diseases and disorders associated with uric acid, including hyperuricemia and gout, in a subject. The disclosure further provides pharmaceutical compositions and methods of treating disorders associated with uric acid, such as hyperuricemia.

METHOD FOR GENERATING A MARKER IN A BIOLOGICAL SAMPLE
20230105306 · 2023-04-06 ·

A method generates a marker in a biological sample including a plurality of cells by means of oligonucleotide constructs. The method includes introducing at least a plurality of first oligonucleotide constructs into the biological sample. The plurality of first oligonucleotide constructs comprise a first promoter, a first nucleic acid sequence encoding a first fluorescent protein, and a first photoremovable cage molecule. The method also includes exposing, in particular scanning, at least a first region of the biological sample with a first spatially constrained light beam to form uncaged first oligonucleotide constructs in order to enable synthesis of first fluorescent proteins from the first nucleic acid sequence and generate at least a part of the marker in the first region of the biological sample.