Nucleic acids delivered by PEGylated cationic liposomes in systemic lupus erythematosus-prone mice: A possible exacerbation of lupus nephritis in the presence of pre-existing anti-nucleic acid antibodies

Nucleic acid-based therapy with plasmid DNA (pDNA) and small interfering RNA (siRNA) have received recent attention for their ability to modulate the cellular expression of genes proteins. Polyethylene glycol-modified (PEGylated) cationic nanoparticles been used as non-viral vectors in vivo delivery these nucleic acids. We reported that PEGylated liposomes (PCL) including pDNA or siRNA induce anti-PEG antibodies upon repeated intravenous injection, leading formation immune complexes enhanced clearance from blood subsequent doses. However, issue surrounding association acids PCL whether induces anti-nucleic acid has not studied. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease character end-organ damage presence anti-nuclear antibodies. healthy mouse an SLE model test hypothesis associated then exacerbate symptoms. report here (pDNA/PCL siRNA/PCL) induced anti-DNA antibodies, respectively, mice. Repeated injections did not, however, cause SLE-like symptoms In addition, SLE-prone mice pre-existing pDNA/PCL were deposited on kidneys exacerbated nephritis complexes. These results may imply do contribute onset individuals who lack but patients