Safety of antisense oligonucleotide and siRNA-based therapeutics.
Oligonucleotide-based therapy is an active area of drug development designed to treat a variety of gene-specific diseases. Two of the more promising platforms are the antisense oligonucleotides (ASOs) and short interfering RNAs (siRNAs), both of which are often directed against similar targets. In light of recent reports on clinical trials of severe thrombocytopenia with two different ASO drugs and increased peripheral neuropathy with an siRNA drug, we compared and contrasted the specific safety characteristics of these two classes of oligonucleotide therapeutic. The objectives were to assess factors that could contribute to the specific toxicities observed with these two classes of promising drugs, and get a better understanding of the potential mechanism(s) responsible for these rare, but serious, adverse events.
Division of Cardiovascular and Renal Products, Office of New Drugs I, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: xuan.chi@fda.hhs.gov.
Xuan
X
Chi
Division of Cardiovascular and Renal Products, Office of New Drugs I, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Philip
P
Gatti
Division of Cardiovascular and Renal Products, Office of New Drugs I, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Thomas
T
Papoian
D000818:Animals; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering