RNase-PON1 fusion polypeptides and related compositions and methods

A fusion polypeptide comprising, from an amino terminal position to a carboxyl terminal position, T-L1-X-L2-P, wherein:

• T is a biologically active RNase, wherein the RNase has at least 95% identity with the amino acid sequence shown in residues 29-156 of SEQ ID NO:22;
• L1 is a first polypeptide linker, wherein L1 is optionally present;
• X is an immunoglobulin heavy chain constant region, wherein the immunoglobulin heavy chain constant region is capable of forming dimers and specifically binding the neonatal Fc receptor (FcRn), wherein the immunoglobulin heavy chain constant region is a human immunoglobulin Fc region;
• L2 is a second polypeptide linker comprising at least eight amino acid residues;
• and
• P is a biologically active paraoxonase, wherein the paraoxonase has at least 95% identity with the amino acid sequence shown in residues 16-355 or 26-355 of SEQ ID NO:6, and wherein the paraoxonase does not contain an amino terminal leader sequence corresponding to residues 1-15 of SEQ ID NO:6;
• wherein the fusion polypeptide comprises an amino acid sequence having at least 95% identity with the amino acid sequence shown in residues 21-740 of SEQ ID NO:48.