Abstract: This disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising a chemically modified cytosine nucleotide. In some embodiments, the dsDNA molecules comprise a therapeutic payload sequence. In some embodiments, the dsDNA molecules are resistant to endonuclease digestion and/or resistant to immune sensor recognition, and supports expression of a therapeutic payload encoded in the dsDNA molecules. The disclosure also provides, for example, pharmaceutical compositions comprising dsDNA molecules comprising a chemically modified cytosine nucleotide.

Abstract: This disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising a chemically modified uridine nucleotide. In some embodiments, the dsDNA molecules comprise a therapeutic payload sequence. In some embodiments, the dsDNA molecules are resistant to endonuclease digestion and/or resistant to immune sensor recognition, and supports expression of a therapeutic payload encoded in the dsDNA molecules. The disclosure also provides, for example, pharmaceutical compositions comprising dsDNA molecules comprising a chemically modified uridine nucleotide.