Mechanistic Understanding for the Greater Sensitivity of Monkeys to Antisense Oligonucleotide–Mediated Complement Activation Compared with Humans

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 351; no. 3; pp. 709 - 717
• Main Authors: Shen, Lijiang, Frazer-Abel, Ashley, Reynolds, Paul R., Giclas, Patricia C., Chappell, Alfred, Pangburn, Michael K., Younis, Husam, Henry, Scott P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: Adolescent; Adult; Amino Acid Sequence; Animals; Complement Activation - drug effects; Complement Activation - physiology; Complement Factor H - genetics; Comprehension; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Macaca fascicularis; Male; Middle Aged; Molecular Sequence Data; Oligonucleotides; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - pharmacology; Oligoribonucleotides - genetics; Oligoribonucleotides - pharmacology; Young Adult; RBC; PS; CFH; SNP; ULN; ASO; EOI; 2′-MOE; AP; ELISA

Differences in sensitivity of monkeys and humans to antisense oligonucleotide (ASO)–induced complement alternative pathway (AP) activation were evaluated in monkeys, humans, and in serum using biochemical assays. Transient AP activation was evident in monkeys at higher doses of two 2′-O-methoxyethyl...