title: Comparative Renal Toxicopathology of Antisense Oligonucleotides.
abstract: This review summarizes the current understanding of nephrotoxicity related to the administration of therapeutic oligonucleotides, particularly those with 2'-methoxy-ethyl (2'-MOE) modifications. To best understand the effects of antisense oligonucleotides (ASOs) on the kidney, the reader should have a general understanding of renal microanatomy, physiology, and general mechanisms related to toxicity, so a short review is presented. Preclinical-clinical correlates are also discussed. Collectively, the data for PS ODN and 2'-MOE-modified ASOs have shown the laboratory animal species utilized in toxicology studies generally overpredict renal effects of these agents. As such, 2'-MOE ASOs do not appear to pose as much of a risk to patients as the preclinical data would suggest. This observation has been confirmed so far in clinical investigations.
authors.affiliation: Pathology and Nonclinical Drug Safety, Ionis Pharmaceuticals, Inc. , Carlsbad, California.
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016376:Oligonucleotides, Antisense / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D016376:Oligonucleotides, Antisense