It is well established that Dicer anchors the 3' end of the substrate in its PAZ domain. Any steric hindrance blocking this interaction would impair Dicer processing. For better understanding on the molecular basis of substrate recognition by Dicer, refer to Narry Kim's 2011 Nature paper (biochemical) and Dinshaw Patel's 2013 Mol Cell paper (structural).
we have done this with the cleavge site modification with cLNA modified siRNA. For details Please see the following references:
1. The R-diastereomer of 6′-O-toluoyl-carba-LNA modification in the core region of siRNA leads to 24-times improved RNA silencing potency against the HIV-1 compared to its Scounterpart J.Chattopadhyaya et al. MedChemComm, 2 (11) 1110-1119 (2011).
2. The carba-LNA modified siRNAs targeting HIV-1 TAR region downregulates HIV-1 replication successfully with Enhanced Potency. J. Chattopadhyaya et al.
Med. Chem. Comm., 2, 206-216 (2011) Hot article
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