Abstract: The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating cystic fibrosis, e.g., in subjects having a mutation resulting in F508del, are described.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating phenylketonuria (PKU) are described.

Abstract: The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating alpha-1 antitrypsin deficiency (AATD) are described.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: The invention provides, inter alia, systems and associated methods, for modifying DNA, such as the genome of a cell. The systems, in certain embodiments, encompass one or more tissue-specific expression-control sequences, such as promoters and microRNA binding sites in addition to a transposase (or a nucleic acid encoding the same) and a template nucleic acid comprising a sequence to be inserted into the genome of a cell, tissue, or subject.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: The disclosure is directed, in part, to improved systems and nucleic acids for modifying target DNA.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: The disclosure provides, e.g., compositions and methods for modulating a host response to a Gene Writer system. In some embodiments, modulation of the host response results in increased integration of a heterologous nucleic acid sequence of interest into a target genome. In some embodiments, modulation of the host response results in an increased stability, e.g., maintenance of an insertion or expression thereof. In some embodiments, modulation of the host response results in decreased cytotoxicity.

Abstract: The invention relates to the use of Argonaute polypeptide:guide molecule complexes as fast and specific nucleic acid probes, as specific, nucleic acid-guided restriction enzymes for DNA and RNA substrates, and as a means to detect RNA-protein interactions, RNA detection, DNA detection, and RNA depletion. Using such Argonaute polypeptide:guide molecule complexes enables fast and specific detection, purification, and enzymatic activity.