Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

The present invention includes a method of increasing, stimulating, inducing, promoting, enhancing or maintaining the genomic stability of a cell of a subject, the method comprising decreasing, reducing, inhibiting, suppressing, limiting or controlling loss of methylation of heterochromatin in the cell and/or modulating heterochromatin dysfunction in a cell of a subject, the method comprising activating, eliciting, stimulate ng, inducing, promoting, increasing or enhancing expression or activity in the cell of one or more DNA methyltransferase (DNMT).

A method for increasing fungal resistance in a plant, a plant part, or a plant cell wherein the method comprises the step of increasing the production and/or accumulation of scopoletin and/or a derivative thereof in the plant, plant part, or plant cell in comparison to a wild type plant, wild type plant part, or wild type plant cell.

Provided herein are, inter alia, compositions and methods for modulating gene expression.

Disclosed herein are methods for N-demethylating an N-methylated compound using an enzymatic reaction, rather than, e.g. a chemical modification. Also provided herein are enzymes for performing the reaction.

A gene editing system is provided that comprises a first nucleotide molecule encoding a dCas9-Ten-Eleven Translocation methylcytosine dioxygenase 1 catalytic domain (TET1CD) fusion protein; and a second nucleotide molecule encoding at least one small guide RNA (sgRNA), comprising: a scaffold region and a spacer region, wherein the spacer region hybridizes to a nucleotide sequence complementary to a target sequence adjacent to a 5′-end of a protospacer adjacent motif (PAM), and wherein the target sequence and the PAM are located within 1 kilobase (kb) of the transcriptional start site (TSS) of the CDKL5 gene. Methods of making and using the system are further described herein.

The invention relates to molecules for controlling plant growth and development. Specifically, the invention relates to molecules comprising a gibberellin activator or a gibberellin inhibitor operably linked to a promoter specific to a lateral organ primordium. The invention also relates to transgenic plants having the transgenic molecules and methods for making such transgenic plants.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

The present invention provides engineered proline hydroxylase polypeptides for the production of hydroxylated compounds, polynucleotides encoding the engineered proline hydroxylases, host cells capable of expressing the engineered proline hydroxylases, and methods of using the engineered proline hydroxylases to prepare compounds useful in the production of active pharmaceutical agents.

The present invention relates to a mutant onion (Allium cepa) plant, which is resistant to a pathogen of viral, bacterial, fungal or oomycete origin. The mutant onion plant has a reduced level, reduced activity or complete absence of AcDMR6 protein as compared to a wild type onion plant.