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.

The present disclosure relates to a Prp8 intein splicing inhibitor. The present disclosure further relates to a method of treating and/or preventing a fungal infection, said method comprising administering a Prp8 intein splicing inhibitor under conditions effective to treat and/or prevent a fungal infection. Also disclosed is a method of inhibiting Prp8 intein expression or activity in a cell or tissue, said method comprising administering a compound under conditions effective to inhibit Prp8 intein expression or activity in a cell or tissue. Further disclosed are methods for screening for compounds that inhibit Prp8 intein splicing comprising an assay and a kit for predicting the likelihood of Prp8 inhibition.