Premium
Inside Cover: 5′‐( E )‐Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA–GalNAc Conjugates (ChemBioChem 11/2016)
Author(s) -
Parmar Rubina,
Willoughby Jennifer L. S.,
Liu Jingxuan,
Foster Donald J.,
Brigham Benjamin,
Theile Christopher S.,
Charisse Klaus,
Akinc Akin,
Guidry Erin,
Pei Yi,
Strapps Walter,
Cancilla Mark,
Stanton Matthew G.,
Rajeev Kallanthottathil G.,
SeppLorenzino Laura,
Manoharan Muthiah,
Meyers Rachel,
Maier Martin A.,
Jadhav Vasant
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600278
Subject(s) - asialoglycoprotein receptor , endocytosis , conjugate , small interfering rna , endosome , gene silencing , chemistry , rna interference , microbiology and biotechnology , biophysics , biochemistry , hepatocyte , rna , in vitro , biology , receptor , gene , mathematical analysis , mathematics
The inside cover picture shows the benefit of 5’‐(E)‐vinylphosphonate (VP), a stable phosphate mimic over 5′‐phosphate (5′‐P) in improving the siRNA‐GalNAc conjugate loading into the RNA‐induced silencing complex (RISC). The siRNA conjugated to trivalent N ‐acetylgalactosamine (GalNAc) is recognized by the asialoglycoprotein receptor (ASGPR) expressed on the surface of a hepatocyte for cellular uptake via endocytosis. Unlike natural phosphate, the 5′‐VP on siRNA‐GalNAc is not removed in endosome/lysosomes. The presence of 5′‐VP on siRNA promotes RISC loading thereby improving the in vivo activity. On the other hand, the loss of 5′‐P from siRNA‐GalNAc hampers RISC loading. More information can be found in the communication by V. Jadhav et al. on page 985 in Issue 11, 2016 (DOI: 10.1002/cbic.201600130).