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: 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: 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.

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.

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.

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.

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

Abstract: Embodiments of the disclosure include implementing a ML-enabled cellular disease model for validating an intervention, identifying patient populations that are likely responders to an intervention, and developing a therapeutic structure-activity relationship screen. To generate a cellular disease model, data is combined from human genetic cohorts, from the literature, and from general-purpose cellular or tissue-level genomic data to unravel the set of factors (e.g., genetic, environmental, cellular factors) that give rise to a particular disease. In vitro cells are engineered using the set of factors to generate training data for training machine learning models that are useful for implementing cellular disease models.