Click-modified anandamide siRNA enables delivery and gene silencing in neuronal and immune cells.
Click chemistry of alkyne-modified RNA with different receptor ligand azides was used to prepare 3'-folate, 3'-cholesterol, and, as a new entity, 3'-anandamide-modified RNA in high yields and excellent purity. The anandamide-modified RNA shows surprisingly high transfection properties and enables the delivery of siRNA even into difficult-to-transfect RBL-2H3 cells which model neuronal uptake. Furthermore, the system was employed in human immune cells (BJAB), demonstrating silencing effects similar to those of a cationic, benchmark transfection reagent. In addition, the anandamide conjugates were found to be nontoxic. The reported chemistry and the described properties of the anandamide siRNA extend the possibilities of using siRNA-based gene silencing in neuronal and immune cells.
Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität , Munich, Germany.
Julian
J
Willibald
Johannes
J
Harder
Konstantin
K
Sparrer
Karl-Klaus
KK
Conzelmann
Thomas
T
Carell
D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry*; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D057930:Click Chemistry; D063388:Endocannabinoids / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D048790:Renilla / Q000201:enzymology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D034741:RNA, Small Interfering; D005492:Folic Acid; D002784:Cholesterol; D008156:Luciferases; C078814:anandamide