The present invention allows a TET1 protein to be more stably expressed in human pluripotent stem cells than in the past by, inter alia, substituting the second amino acid from the amino terminal of a TET1 protein with a different amino acid. Furthermore, upon differentiation of said pluripotent stem cells, it is possible to quickly eliminate the expression of, inter alia, NANOG, which is an inhibitor of differentiation and promote the expression of factors related to differentiation by introducing a variant TET1 protein to a pluripotent stem cell. The present invention provides a method for manufacturing pluripotent stem cells with increased differentiation potential, and a substance that is useful to said method.

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.

Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems.

The present invention relates to a mutant Brassica plant, which is resistant to a pathogen of viral, bacterial, fungal or oomycete origin. The mutant Brassica plant has a reduced level, reduced activity or complete absence of DMR6-1 protein and DMR6-2 protein as compared to a wild type Brassica plant.

Disclosed are compositions and methods for modulating cancer stem cells. More particularly, the present invention discloses the use of lysine demethylase (LSD) inhibitors and protein kinase C theta inhibitors (PKC-) for inhibiting the growth of LSD- and/or PKC--overexpressing cells including cancer stem cells, for enhancing the biological effects of chemotherapeutic drugs or irradiation on cancer cells, for treating cancer, including non-metastatic and metastatic cancer and/or for preventing cancer recurrence.

Many studies have shown that CRISPR-Cas nucleases can tolerate up to five mismatches and still cleave; it is hard to predict the effects of any given single or combination of mismatches on activity. Taken together, these nucleases can show significant off-target effects but it can be challenging to predict these sites. Described herein are methods for increasing the specificity of genome editing using the CRISPR/Cas system, e.g., using RNA-guided FokI Nucleases (RFNs), e.g., FokI-Cas9 or FokI-dCas9-based fusion proteins.

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 provides a method of producing astaxanthin and lysine in recombinant gram-positive bacteria comprising a nucleic acid sequence encoding for a crtZ-protein from F. pelagi and comprises a nucleic acid sequence encoding for a crtW-protein.

The invention provides methods for activating a repressed allele within an imprinting control region, thereby treating an imprinting associated disorder.

This disclosure concerns compositions and methods for targeting peptides, polypeptides, and proteins to plastids of plastid-containing cells. In some embodiments, the disclosure concerns chloroplast transit peptides that may direct a polypeptide to a plastid, and nucleic acid molecules encoding the same. In some embodiments, the disclosure concerns methods for producing a transgenic plant material (e.g., a transgenic plant) comprising a chloroplast transit peptide, as well as plant materials produced by such methods, and plant commodity products produced therefrom.