The present invention relates to compositions and methods for the inhibition of the infectivity of a herpesvirus. In certain embodiments, the compositions and methods provide a CRISPR-associated peptide and a guide nucleic acid, which induce the mutation of herpesvirus genome, thereby inhibiting the infectivity of the herpesvirus. Further disclosed are Cas peptides including Cas9 or a variant thereof comprising one or more point mutations relative to wildtype Streptococcus pyogenes Cas 9 (spCas9), and Cpf1 or a variant thereof.

Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.

The present invention generally relates to systems, methods and compositions used for the control of gene expression involving sequence targeting, such as genome perturbation or gene-editing, that may use vector systems related to recombinases and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and components thereof.

The present application provides materials and methods for treating a patient with a titin-based myopathy, particularly a titin-based cardiomyopathy, and/or other titinopathy. In addition, the present application provides materials and methods for editing the titin gene in a cell by genome editing.

The invention provides methods and means for specifically altering the DNA sequence in a genome, in particular for genome editing by deleting or replacing a sequence of interest. Advantageously, the invention uses two non-identical sequences naturally occurring in a genome as target sites two which DNA-recombining enzymes are generated. The invention is in particular useful for medicine, in particular to repair a mutation in a genome or to delete predefined genetic material from cells or tissue and to cure diseases. An advantage of the invention is that it allows precise site directed altering of DNA without engaging host DNA repair pathways and thereby works without inducing random insertions and deletions (in-dels).

Presented herein is a high-throughput (HTP) genomic engineering platform for improving the production of therapeutic proteins in Chinese hamster ovary (CHO) cells. The disclosed HTP genomic engineering platform is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. The platform utilizes a unique suite of HTP genetic engineering tools to explore the genomic landscape associated with therapeutic protein production pathways, in order to unravel the biological drivers and disentangle the uncharacterized genetic architecture responsible for optimizing therapeutic protein production in CHO cells.

The present disclosure provides shuttle vectors for editing exogenous polynucleotides in heterologous live cells, as well as automated methods, modules, and multi-module cell editing instruments and systems for performing the editing methods.

The present invention relates to an engineered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system comprising engineered dual guide nucleic acids (e.g., RNAs) capable of activating a CRISPR-Associated (Cas) nuclease, such as a type V-A Cas nuclease. Also provided are methods of targeting, editing, and/or modifying a nucleic acid using the engineered CRISPR system, and compositions and cells comprising the engineered CRISPR system.

The present invention provides modified stem cells (SCs) and use of the SCs to treat disease.