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- W2810843485 abstract "This chapter reviews the proinflammatory effects of antisense oligonucleotide (ASO) therapies as a class effect of these drugs. Early in drug development, induction of immune responses such as activation of the alternate complement pathway and induction of cytokines and splenomegaly in animals were observed. Some species were more sensitive for these ASO-induced effects than other species. A key step was the identification of immunostimulatory sequences contained in ASO that recognize innate immune receptors, leading to the induction of proinflammatory responses. ASOs are in development as therapies that leverage this immunostimulatory effect, whereas for other ASO, immune activation effects are undesired side effects. Although elimination of these immunostimulatory sequences from ASO candidates lessened some of the effects, or required higher dose of ASO for the induction of the effects, there remain proinflammatory class effects associated with ASO. Steps aimed at derisking ASO drug candidates during the screening process to optimize safe therapeutics in clinical trials are discussed." @default.
- W2810843485 created "2018-07-10" @default.
- W2810843485 creator A5091767332 @default.
- W2810843485 date "2018-06-15" @default.
- W2810843485 modified "2023-09-24" @default.
- W2810843485 title "Class-Related Proinflammatory Effects" @default.
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- W2810843485 doi "https://doi.org/10.1002/9781119070153.ch8" @default.
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