Abstract: Described and provided are adenosine base editors and compositions comprising adenosine base editors that have increased efficiency. Also described and provided are methods of using base editors comprising adenosine deaminase variants for altering mutations associated with Glycogen Storage Disease Type 1a (GSD1a).

Abstract: The present invention provides, among other things, a method of producing a synthetic RNA using a self-templating approach. For example, in some embodiments a synthetic gRNA is produced comprising: contacting a first RNA with a second RNA, wherein the first RNA and the second RNA comprise at least five RNA nucleotides that are complementary, and wherein the contacting forms a stem structure or a stem loop structure, and ligating the first RNA and the second RNA with a ligating enzyme (i) within the stem structure, or (ii) at an end of the stem structure, thereby forming a loop at the end of the stem structure.

Abstract: Provided herein are prime editing systems featuring prime editors complexed with a chimeric prime editing (PE) guide polynucleotide. Systems, prime editor fusion proteins and methods of using such editors for editing a double-stranded DNA target sequence are also provided.