The invention provides compositions and methods for high-efficiency genome editing. In some aspects, the invention provides retron-guide RNA cassettes and vectors comprising the cassettes. Also provided are host cells that have been transformed with the vectors. In other aspects, the invention provides retron donor DNA-guide molecules. In some other aspects, methods for genome editing and the screening of genetic loci are provided. In further aspects, methods and compositions are provided for the prevention or treatment of genetic diseases. Kits for genome editing and screening are also provided.

Methods and compositions for modulating the activities of connexins are provided, including, for example, for use in post-surgical, trauma, or tissue engineering applications. These compounds and methods can be used therapeutically, for example, to reduce the severity of adverse effects associated diseases and disorders where localized disruption in direct cell-cell communication is desirable.

Disclosed herein are glutathione-sensitive oligonucleotides and methods of using the same. The glutathione-sensitive oligonucleotides may comprise at least one nucleotide represented by Formula I: ##STR00001##
wherein A, B, I, J, L, R.sub.1, R.sub.2, R.sub.3, R.sub.4, U.sub.1, U.sub.2, W, and X are as defined in the specification. An illustrative glutathione-sensitive oligonucleotide of the disclosure may have the following chemical structure: ##STR00002##
Any oligonucleotide of interest may be modified with a glutathione-sensitive moiety, including oligonucleotides used for in vivo delivery, such as nucleic acid inhibitor molecules. Also disclosed are glutathione-sensitive nucleotide and nucleoside monomers, including glutathione-sensitive nucleoside phosphoramidites that can be used, for example, in standard oligonucleotide synthesis methods. In addition, glutathione-sensitive nucleotide and nucleoside monomers without a phosphoramidite can be used therapeutically, for example, as anti-viral agents.

Provided are methods for editing RNA by introducing a deaminase-recruiting RNA in a host cell for deamination of an adenosine in a target RNA, deaminase-recruiting RNAs used in the RNA editing methods, compositions and kits comprising the same.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Provided herein, among other things, is an automatable procedure that employs in vitro directed evolution to create DNA sequences that encode a ligand-responsive ribozyme and which, when transcribed, can control expression of genes they are coupled to. The method also allows creation of functional RNA sequences that bind target molecules, without requiring any modification or immobilization of the target.

Compositions for protecting subjects from diseases caused by (+) SS RNA virus are described herein. The compositions include (i) a vector containing a DNA encoding a RNA molecule of an infectious (+) SS RNA virus operably linked to a eukaryotic RNA polymerase promoter and a carrier; or (ii) (+) SS RNA viruses obtained from eukaryotic cells transfected with the vector of (i) and a carrier.

Provided is a metastasis suppressing agent containing a HSP47 inhibitor.

Methods and compositions for treating cholangiocarcinoma.

A transfection reagent composition comprising: 30-60 MOL % of an cationic lipid, or pharmaceutical acceptable salt thereof; 10-60 MOL % structural lipid; a sterol and 0.1 to about 10 MOL % of a stabilizing agent is provided. The reagent is particularly adapted for neuron and related cell types. A method of manufacturing LNP including nucleic acid for selective uptake into either neurons or astrocytes or neural progenitor cells is also provided.