Evolutionary Design and Experimental Evaluation of Selective Hammerhead Ribozymes

this paper describes, in brief, an evolutionary algorithm (EA) for the design of RNA-activated hammerhead ribozymes that selectively cleave a mutant transcript, while leaving the wild type transcript largely unaffected. We present experimental data that provide clear evidence of the selective silencing of the PABPNI gene, at both mRNA and protein levels. As such, this work presents a concrete example of the employability of machine learning algorithms (here, EAs) for the design of trans-acting ribozymes capable of gene silencing via selective mRNA cleavage.