Abstract: Nonnaturally occurring host cells altered to increase their ability to transfer genetic molecules into the host cells as compared to an unaltered host cell are provided. Also provided are methods for identifying endogenous loci of a host cell which inhibit transformation efficiency and/or electroporation of genetic molecules into the cell as well as methods for producing nonnaturally occurring host cells with enhanced transformation efficiency and/or the modified ability to allow for genomic integration of an exogenous DNA sequence via electroporation. Methods for producing biochemicals and products produced with the nonnaturally occurring host cells are also provided.

Abstract: Eukaryotic cells and related reagents, systems, methods, and compositions for increasing the frequency of homology directed repair (HDR) of target editing sites with genome editing molecules are provided.

Abstract: This disclosure provides non-naturally occurring collagen and elastin molecules. The non-naturally occurring collagens and elastins include truncated collagens, truncated elastins, as well as fusion proteins thereof. The non-naturally occurring collagen and elastin are useful in foods, cosmetics and many other products and uses.

Abstract: The present invention provides novel mRNA elements capable of forming hairpin, double-stranded RNA structures independent of other non-coding RNAs. These mRNAs are stably expressed, lack polyadenylation tails, and allow minimal protein translation except when in the presence of specific proteins. Also provided, are compositions and kits comprising the mRNA element, as well as methods for its use in the regulation of protein translation. Advantageously, the disclosed elements represent a novel tool useful in regulating the expression of a wide variety of proteins of interest.

Abstract: Disclosed herein are genome editing systems and compositions that target a cystic fibrosis transmembrane conductance regulator (CFTR) gene and a sodium channel epithelial 1 alpha (SCNN1A) gene, comprising a Cas9 molecule, and a gRNA molecule comprising a targeting domain that is complementary with a target sequence of a CFTR gene or a SCNN1A gene, and cells comprising such genome editing systems and compositions. Also provided are methods for using the genome editing systems, compositions, and cells for genome engineering (e.g., altering a CFTR gene and/or a SCNN1A gene), and for preventing or treating Cystic Fibrosis (CF) and CF-like disease.

Abstract: CRISPR/Cas-related compositions and methods for treatment of Usher Syndrome and/or Retinitis Pigmentosa are disclosed herein.

Abstract: The present invention relates to compositions comprising and methods of using synthetic polynucleotides, e.g., modified mRNA, encoding CRISPR related proteins including dCAS9 and synthetic sgRNAs targeting a gene of interest.

Abstract: Pre-existing alloreactive memory T cells are a major barrier to the induction of allograft tolerance in organ transplant recipients. The use of Eomesodermin (Eomes) expression in memory T cells to determine the risk of allograft rejection in a subject is described. Also described is the use of Eomes expression in memory T cells of transplant recipients to modify immunosuppressive therapy.

Abstract: The disclosure includes the identification and use of gene expression profiles, or patterns, with clinical relevance to cancer. In particular, the disclosure includes the identities of genes that are expressed in correlation with tumor grade. The levels of gene expression are disclosed as a molecular index for determining tumor grade in a patient and predicting clinical outcome, and so prognosis, for the patient. The molecular grading of cancer may optionally be used in combination with a second molecular index for diagnosing cancer and its prognosis. The disclosure further includes methods for predicting cancer recurrence, and/or predicting occurrence of metastatic cancer. For diagnosis or prognosis, the disclosure further includes methods for determining or selecting the treatment of cancer based upon the likelihood of life expectancy, cancer recurrence, and/or cancer metastasis.

Abstract: The present disclosure relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present disclosure relates to RAF gene fusions as diagnostic markers and clinical targets for cancer.

Abstract: Methods for in vitro transcription and translation using a double-stranded concatemeric DNA in a eukaryotic cell-free expression system are provided. The method includes the steps of (a) contacting a double-stranded concatemeric DNA with a eukaryotic cell-free expression system, and (b) expressing a protein in vitro from the double-stranded concatemeric DNA in the eukaryotic cell-free expression system. The double-stranded concatemeric DNA includes a plurality of tandem repeat sequences. The plurality of tandem repeat sequences includes an expression sequence including a promoter, a cap-independent translation element (CITE), and an open reading frame. A final concentration of the double-stranded concatemeric DNA in the eukaryotic cell-free expression system is in a range from about 0.1 ng/?L to about 35 ng/?L. A RCA product DNA may be used as the double stranded concatemer DNA for the methods.

Abstract: Provided herein are compositions and methods related to targeted delivery of a therapeutic or diagnostic agent to a subject utilizing an engineered receptor-ligand system, such as an engineered dockerin-cohesin system. As described herein, previously-developed targeted delivery systems for delivering therapeutic and diagnostic agents to a tissue of interest have drawbacks that have not been addressed to date. For example, with respect to the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), both of which hamper delivery of agents to the brain, others have relied on the use of endogenously expressed receptors, like the transferrin receptor, to assist the agent across the barriers.

Abstract: Described herein are biological devices and methods for using the same to produce a polyactive carbohydrate. The biological devices include microbial cells transformed with a DNA construct containing genes for producing a chitin synthase, a chitosanase, and a chitin deacetylase. In some instances, the biological devices also include a gene for lipase. Methods for using the polyactive carbohydrate are also provided herein, including, but not limited to, enhancing the physiological properties of plants; medical applications; applications in the construction, materials science, and home goods industries; personal care, grooming, cosmetics, and oral care compositions containing the polyactive carbohydrate; methods for water decontamination; and the production of polyurethanes.

Abstract: The present application provides materials and methods for treating a patient with autosomal dominant CORD, both ex vivo and in vivo; materials and methods for editing a GUCY2D gene in a human cell; and materials and methods for editing a R838H, R838C, or R838S mutation in a GUCY2D gene in a human cell. The present application also provides one or more gRNAs or sgRNAs for editing a GUCY2D gene; one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene. The present application provides a therapeutic for treating a patient with autosomal dominant CORD. The present application also provides a kit for treating a patient with autosomal dominant CORD. In addition, the present application provides a self-inactivating CRISPR-Cas system.

Abstract: The present invention relates to a new method for successfully inducing the mutation of cell chemokine receptor CCR5 gene into CCR5?32 deletion gene by using the CRISPR-Cas9 genome editing technique. CCR5 is an important co-receptor for entry of Human Immunodeficiency Virus (HIV) into human host cells. CCR5?32 deletion is a 32-bp deletion in CCR5 coding region, which results in change and premature termination in the sequence following the 185th amino acid. Biallelic homozygous deletion of CCR5?32 is naturally resistant to HIV infection, i.e., the people carrying this mutation can't be infected by HIV. The present invention uses both lentiviral packaging system and the CRISPR technique to induce CCR5?32 deletion. Due to the characteristics of a wide range of Lentivirus infection, the invention can be applied to cells such as bone marrow stem cells and CD4+ T cells and can be expected to be the therapeutic drug for HIV/AIDS infection or other diseases.

Abstract: The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Abstract: The specification relates generally to methods of detecting, diagnosing, and/or identifying pathogens, e.g., infectious disease pathogens and determining their drug sensitivity and appropriate methods of treatment. This invention also relates generally to methods of monitoring pathogen infection in individual subjects as well as larger populations of subjects.

Abstract: Provided herein are cell penetrating conjugates. The conjugates include a non-cell penetrating protein attached to a phosphorothioate nucleic acid or phosphorothioate polymer backbone, wherein the phosphorothioate nucleic acid or phosphorothioate polymer backbone enhances intracellular delivery of the non-cell penetrating protein. Also provided are compositions and kits comprising the cojugates.

Abstract: This document provides methods and materials for treating diabetes. For example, methods and materials for using nucleic acid encoding human preproinsulin to treat diabetes (e.g., type I or type II diabetes) are provided.

Abstract: The invention provides methods for determining the mutation burden of a tumor by assaying tumor DNA that is representative of genetic loci that are themselves representative of genetics of the tumor. The assayed tumor DNA may be itself agnostic as to loci, so long as it is representative of loci that are representative of tumor mutation burden. The invention provides for assays in which the tumor DNA being sequenced or tested can be something other than, and possibly less than, a full panel of oncogenes that is expected to stand for a tumor's mutational load.