Overview

AmiRNAs have advantages over other RNAi tools in terms of gene silencing specificity and lower off-target effects. However, only precise processing of amiRNAs using Drosha and Dicer ensures efficient and safe siRNAs. Since the sequence, structure and variability of pri-miRNA structure strongly affect its processing, it is difficult to predict the effects of replacing miRNA with an exogenous siRNA sequence. Inappropriate amiRNA design can result in inefficient processing, generation of siRNA variants with seed sequence changes, or induction of arm switching - a process that leads to the release of the passenger strand of the siRNA. However, it has been shown possible to change the 21-nt sequence of a mature miRNA in a natural miRNA precursor without affecting miRNA biogenesis and maturation, opening the prospect of designing amiRNAs with new targets.

miRarchitect was created to support the rational design of amiRNA therapeutics. The design process uses state-of-the-art computational techniques, including machine learning, and performs analysis of the target sequence (input data), design and study of siRNA structure and thermodynamics, selection of the best native pri-miRNA scaffold, and amiRNA generation.

Team

miRarchitect tool is managed by researchers at the Department of Genome Engineering and at the Department of Structural Bioinformatic, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland and Institute of Computing Science, Poznan University of Technology, Poznan, Poland.