Methods and compositions for modulation of the activity of alpha thalassemia/mental retardation syndrome X-linked (ATRX), e.g., modulation of DNA-ATRX or RNA-ATRX interactions, and methods for identifying and using compounds that modulate DNA-ATRX or RNA-ATRX interactions, as well as the compounds themselves.

The present specification provides compositions and methods that are capable of directly installing an insertion or deletion of a given nucleotide at a specified genetic locus. The compositions and methods involve the novel combination of the use an engineered RNA enzyme (i.e., “ribozyme”) that is capable of site-specifically inserting or deleting a single nucleotide at a genetic locus and the use of a nucleic acid programmable DNA binding protein (napDNAbp) (e.g., Cas9) to target the engineered ribozyme to a specified genetic locus, thereby allowing for the direct installation of an insertion of deletion at the specified genetic locus by the engineered ribozyme.

Method of generating a barcoded library, comprising delivering a polynucleotide into a cell, each polynucleotide comprising: (i) a sequence encoding a barcoding construct operably linked to a first promoter that is an antisense promoter, wherein the barcoding construct comprises a trans-splicing element and a barcode sequence; and a sequence encoding a perturbation element operably linked to a second promoter; generating RNA transcripts of the polynucleotide delivered into the cell, wherein the RNA transcripts comprise the barcoding construct and the perturbation element; and splicing the barcoding sequence onto endogenous RNA molecules in the cell, thereby generating a barcoded library, each member of the barcoded library comprising the barcode sequence and the endogenous RNA molecule attached with the barcode sequence.

The present invention relates to a recombinant adenovirus with increased in-vivo safety, tissue specificity, and anticancer activities, and a use thereof. Specifically, the recombinant adenovirus comprising: a promoter of the liver tissue-specific phosphoenolpyruvate carboxykinase (PEPCK) gene; a trans-splicing ribozyme which is operably linked to the promoter and acts on a cancer-specific gene; a therapeutic gene or a reporter gene which is linked to the 3 exon of the ribozyme; and a serotype 35 fiber knob and a serotype 5 shaft, in which the orf4 gene is deleted from adenovirus E1, E3 and E4 orf1, shows remarkable in-vivo safety, high specificity for a target tissue, and remarkable anticancer effects, and thus can be useful for an anticancer drug or a cancer diagnostic agent as a gene delivery vector.