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Article
Open AccessRational design of a JAK1-selective siRNA inhibitor for the modulation of autoimmunity in the skin
Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety prof...
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Article
Open AccessChemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington’s disease models
Small interfering RNAs are a new class of drugs, exhibiting sequence-driven, potent, and sustained silencing of gene expression in vivo. We recently demonstrated that siRNA chemical architectures can be optimi...
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Article
A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system
Sustained silencing of gene expression throughout the brain using small interfering RNAs (siRNAs) has not been achieved. Here we describe an siRNA architecture, divalent siRNA (di-siRNA), that supports potent,...
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Article
RNAi modulation of placental sFLT1 for the treatment of preeclampsia
Preeclampsia, a hypertension condition with no approved therapies, is treated in monkeys by gene silencing in the placenta.
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Article
Open AccessHeavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing
RNA-based drugs depend on chemical modifications to increase potency and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics ...
