Abstract: Compositions and methods for reducing complement activation by introducing one or more alterations into a complement component 3 (C3) polynucleotide in a cell. In particular embodiments, the disclosure features a base editor system (e.g., a fusion protein or complex comprising a programmable DNA binding protein, a nucleobase editor, and gRNA) for modifying a C3 polynucleotide, where the modification is associated with reduced expression, and/or reduced activity of the C3 polypeptide encoded by the polynucleotide.

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.