Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation

Second-generation (Gen 2) Antisense oligonucleotides (ASOs) show increased nuclease stability and affinity for their RNA targets, which has translated to improved potency and therapeutic index in the clinic. Gen 2 ASOs are typically modified using the phosphorothioate (PS) backbone modification, whi...

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Veröffentlicht in:	Nucleic acid therapeutics 2018-04, Vol.28 (2), p.86-96
Hauptverfasser:	Miller, Colton M., Wan, W. Brad, Seth, Punit P., Harris, Edward N.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antisense oligonucleotides Biochemistry Cell Adhesion Molecules, Neuronal - genetics Cell Adhesion Molecules, Neuronal - metabolism Cell surface Compartments Deoxyribonucleic acid DNA Docosahexaenoic Acids - pharmacology Endocytosis Endocytosis - drug effects Endosomes - drug effects Endothelial cells HEK293 Cells Hepatocytes Humans Internalization Kinases Liver Maturation Nuclease Oligonucleotides Oligonucleotides, Antisense - chemical synthesis Oligonucleotides, Antisense - genetics Oligonucleotides, Antisense - metabolism Original Original Articles Pharmaceuticals Phosphorothioate Phosphorothioate Oligonucleotides - chemical synthesis Phosphorothioate Oligonucleotides - genetics Phosphorothioate Oligonucleotides - metabolism Proteins rab GTP-Binding Proteins - genetics rab GTP-Binding Proteins - metabolism rab5 GTP-Binding Proteins - genetics rab5 GTP-Binding Proteins - metabolism Receptors Receptors, Lymphocyte Homing - genetics Receptors, Lymphocyte Homing - metabolism Ribonucleic acid RNA RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Signal transduction Spleen Translocation Vesicular Transport Proteins - genetics Vesicular Transport Proteins - metabolism
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