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.
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