Provided herein are methods and compositions for treatment and/or prevention of liver disease. Aspects of the present disclosure relate to the engineering of a quiescent Hepatic Stellate Cell, and use of the engineered quiescent Hepatic Stellate Cell, or population thereof in the treatment and/or prevention of liver disease.

The invention provides propagator cells and methods for propagating phage and transduction particles.

The invention describes a novel system for identifying optimized gRNAs for use in CRISPR/Cas9 genome editing platforms. The invention allows for the determination of specific gene alterations rendered by a particular gRNA, thereby permitting the generation of optimized gRNA libraries.

In alternative embodiments, provided herein are transcription/translation (TX-TL) systems and methods of using them for use as rapid prototyping platforms for the synthesis, modification and identification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites, from biosynthetic gene cluster pipelines. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the combinatorial biosynthesis of natural products (NPs), natural product analogs (NPAs) and secondary metabolites. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the rapid prototyping of complex biosynthetic pathways as a way to rapidly assess combinatorial and biosynthetic designs before moving to cellular hosts. In alternative embodiments, these exemplary TX-TL systems are multiplexed for high-throughput (HT) automation and for prototyping engineered platforms for the synthesis or modification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites analogs.

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

The invention provides methods of treating polyglutamine diseases, e.g., spinocerebellar ataxia Type 6, in a subject, comprising administering to the subject an IRES inhibitor in an amount effective for treating the SCA6 in the subject. Also provided herein are the IRES inhibitors, and pharmaceutical compositions comprising the same.

The invention discloses the use of single-stranded RNA toeholds of different lengths to promote the re-association of various RNA-DNA hybrids, which results in activation of multiple split functionalities inside human cells. Previously designed RNA/DNA nanoparticles employed single-stranded DNA toeholds to initiate re-association. The use of RNA toeholds is advantageous because of the simpler design rules, the shorter toeholds, and the smaller size of the resulting nanoparticles compared to the same hybrid nanoparticles with single-stranded DNA toeholds. Moreover, the co-transcriptional assemblies result in higher yields for hybrid nanoparticles with ssRNA toeholds.

The disclosure provides novel personalized therapies, kits, transmittable forms of information and methods for use in treating patients having cancer, wherein the cancer is amenable to therapeutic treatment with an inhibitor, e.g., an inhibitor of any of the targets disclosed herein. Kits, methods of screening for candidate inhibitors, and associated methods of treatment are also provided.

Provided herein are methods and compositions for treatment and/or prevention of liver disease. Aspects of the present disclosure relate to the engineering of a quiescent Hepatic Stellate Cell, and use of the engineered quiescent Hepatic Stellate Cell, or population thereof in the treatment and/or prevention of liver disease.

The present invention provides an in vitro synthesis method for an sgRNA and a kit thereof. Specifically, the present invention provides a nucleic acid construct having a structure represented by formula I from 5′ to 3′: Y1-L1-Y2-L2-Y3-Y4 (I), wherein Y1 is an RNA polymerase promoter region; L1 is absent or a linking sequence; Y2 is a target DNA sequence; L2 is absent or a linking sequence; Y3 is a downstream primer binding region; Y4 is absent or a nucleotide sequence; and each “-” is independently a bond or a nucleotide linking sequence.