The quest for the best dsRNA target sequences – Genome wide screen and sequence tinkering

RNAi based pest control holds big promises for species-specific pest control. One of the challenges is the identification of the best RNAi target sequences, i.e. those that lead to the death of the target at minimal concentrations and with minimal side effects on other species. The difficulty in performing large-scale screens in pest species has limited the number of genes that could be tested. Genetic model systems are more easily subjected to genome wide RNAi screens, but it has remained an open question, in how far target genes identified in one species can be transferred to other species.
In a genome wide RNAi screen, we have identified the most efficient RNAi target genes in the red flour beetle Tribolium castaneum. We present the results of that screen and show, what we learned about good target genes in our ongoing follow-up analyses. Further, we will discuss our efforts in transferring RNAi target genes to other pest species, where we and others find quite some variability. We will also discuss our efforts to modify the sequences for increasing efficiency and for adapting species-specificity.

At the end, we will give a brief perspective on a reasonable approach for identification of the best target genes based on our findings.