The present invention relates to a cell capable of producing a fluorinated, a chlorinated or a brominated compound, methods for producing fluorinated, chlorinated or brominated compounds in a cell and expression systems therefor.

The present invention generally relates to therapeutic inhibition of protein arginine methyltransferase 5 (PRMT5). In particular, cell lines having MTAP loss and increased intracellular MTA concentrations show selective dependence on PRMT5. Thus, the invention also relates to methods of identifying and treating PRMT5-related diseases in subjects or tissues which have an MTAP deficiency, alone or in combination, with a second agent that reduces MTAP activity and/or increases intracellular MTA levels, and/or provides an MTA analogs to the cell or tissue. The invention also relates to the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas System and components thereof. More specifically, the present invention relates to the delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions in tumor cells ex vivo and/or in vivo. For example using methods disclosed herein, cells can be sensitized to PRMT5 inhibition.

The present invention generally related to a modified microbial cell capable of producing high levels of spermidine and/spermidine derivatives. The genetically modified microbial cell comprises at least one modification to native spermidine biosynthetic pathway via putrescine together with genes involved in the S-adenosylmethionine biosyntheticpathway.

Provided herein, among other things, is an engineered non-plant cell that produces a tropane alkaloid product, a precursor of a tropane alkaloid product, or a derivative of a tropane alkaloid product. A method for producing a tropane alkaloid, a precursor of a tropane alkaloid product, or a derivative of a tropane alkaloid product that makes use of the cell is also described.

The present specification relates to methods of treatment of wild type MTAP gene cancers comprising administering a MTA synergistic PRMT5 inhibitor to a patient in need thereof.