Compositions and methods for reducing complement activation by introducing one or more alterations into a complement factor B (CFB) polynucleotide in a cell. In particular embodiments, the invention of 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 CFB polynucleotide, where the modification is associated with reduced expression, and/or reduced activity of the CFB polypeptide encoded by the polynucleotide.