A chimeric molecule of one or more proteins or peptides fused, complexed or linked to one or more anionic molecules. Efficient in vitro and in vivo delivery is attained by encapsulating these molecules in cationic lipids or cationic liposomes. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

A family of structurally related proteins has been found to have enzymatic activity. The protein family may comprise DUF1874 proteins. Members of this family can be used to modulate the structure, function and/or activity of a cellular signalling molecule that is associated with a cellular antiviral response. In particular, the proteins described herein exhibit an ability to modulate the function, structure and/or activity of cyclic oligoadenylate (cOA); that is to say they can be used to inhibit, destroy, ablate and/or breakdown cOA activity, structure and/or function. The disclosed proteins (all of which belong to the DUF1874 protein family) are generally referred to as “ring nucleases”.

A vector production system is provided. The system comprises recombinant cells designed to encode at least a first recombinase under the control of an inducible promoter and the cells include an expression vector encoding a nucleic acid of interest within the regulatory elements of the expression vector which are flanked on either side by a target sequence for at least the first recombinase. The vector production system provides an efficient one-step process for producing linear or circular covalently closed vectors that incorporate a nucleic acid sequence of interest.

The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the installation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.

The present invention relates to lipase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

The present disclosure includes the production of a mutant plant resistant to an herbicide of the phosphonomethylglycine family, e.g. glyphosate. Compositions and methods are provided for editing a nucleotide sequence of interest in a cell employing a guide polynucleotide/Cas endonuclease system, wherein the Cas endonuclease is guided by a guide polynucleotide to recognize and optionally introduce a double strand break at a specific target site into the genome of a cell. The nucleotide sequence of interest to be edited can be located within or outside the target site that is recognized by a Cas endonuclease. More specifically, compositions and methods are provided for editing an enolpyruvylshikimate-3-phosphate synthase (EPSPS) nucleotide sequence in a cell. The methods and compositions employ a guide polynucleotide/Cas endonuclease system to provide for an effective system for editing EPSPS nucleotide sequences of within the genome of a cell. Also provided are compositions and methods for the production of glyphosate tolerant plant cells, plants explants, seeds and grain.

The present invention relates to a composition comprising a) recombinant exosporium-producing Baciillus cells that express a fusion protein comprising: (i) at least one plant growth stimulating protein or peptide and (ii) a targeting sequence that localizes the fusion protein to the exosporium of the Baciillus cells; and b) at least one particular fungicide disclosed herein in a synergistically effective amount. Furthermore, the present invention relates to the use of this composition as well as a method for enhancing plant growth, promoting plant health, and/or reducing overall damage of plants and plant parts.

RNA molecules comprising a guide sequence portion having 17-20 nucleotides in the sequence of 17-20 contiguous nucleotides set forth in any one of SEQ ID NOs: 1-3010 and compositions, methods, and uses thereof.

The present disclosure provides methods and kits for generating recombinant bacteriophage genomes.