A system for editing of a target sequence at a locus of a host cell is disclosed. The system has a nucleic acid molecule comprising a nucleic acid segment comprising a targeting RNA sequence and an RNA segment that binds a protein. The system also has a nucleic acid molecule comprising a nucleic acid segment encoding a polypeptide with endonuclease activity fused to a protein that binds the RNA segment. The system also comprises a double stranded DNA molecule comprising DNA comprising at least one nucleotide sequence that is capable of binding to the target sequence at the locus.

Fusion constructs encoding RNase-H-like domain containing compositions are disclosed. Disclosed are also compositions and methods utilizing RNase-H-like domain containing compositions for the treatment of cancer. Also disclosed are the methods of making and using the RNase-H-like domain containing compositions in treating various diseases, conditions, and cancer.

Compositions and methods comprising novel deaminase polypeptides for targeted editing of nucleic acids are provided. Compositions comprise deaminase polypeptides. Also provided are fusion proteins comprising a DNA-binding polypeptide and a deaminase of the invention. The fusion proteins include RNA-guided nucleases fused to deaminases, optionally in complex with guide RNAs. Compositions also include nucleic acid molecules encoding the deaminases or the fusion proteins. Vectors and host cells comprising the nucleic acid molecules encoding the deaminases or the fusion proteins are also provided.

Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.

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

A factor that is caused by a nucleic acid and influences the kinetics of an extracellular vesicle is screened. A library of barcoded extracellular vesicles is provided.

Provided herein are fusion proteins, isolated nucleic acids encoding a fusion protein, and gene delivery vectors comprising the same, wherein the isolated nucleic acids comprise: (i) a first sequence encoding a RNA-binding zinc finger domain; and (ii) a second sequence encoding a fusion partner; and methods of using the same.

Described herein are compositions and methods for modulating protein abundance in a target-specific manner via degron tags.

The disclosure provides systems, methods, and compositions for a target specific nuclease and a blunting enzyme to correct frameshift mutations for genome editing and treatment of diseases. In some embodiments, the target specific nuclease and the blunting enzyme are combined with a guide RNA and/or a microhomology-mediated end joining (MMEJ) inhibitor.

A method for re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO based on an inactivated CRISPR-based system and a DNA dioxygenase as well as a gRNA guiding the construct to the RASAL1, LRFN2, and KLOTHO gene for demethylation of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO, in particular, hypermethylated RASAL1, LRFN2, and KLOTHO promoter, thus, allowing re-expression of RASAL1, LRFN2, and KLOTHO for the treatment of fibrosis, cancer or neuronal disorders in a subject is provided. A kit of parts for allowing re-expression of hypermethylated RASAL1, hypermethylated LRFN2, and hypermethylated KLOTHO in a subject, a vector or vector system, and nucleic acid constructs are also provided.