 Extensive efforts in computational biology have been directed toward the design of successful dsRNA reagents that maximize gene knockdown but minimize " off @-@ target " effects . Off @-@ target effects arise when an introduced RNA has a base sequence that can pair with and thus reduce the expression of multiple genes . Such problems occur more frequently when the dsRNA contains repetitive sequences . It has been estimated from studying the genomes of humans , C. elegans and S. pombe that about 10 % of possible siRNAs have substantial off @-@ target effects . A multitude of software tools have been developed implementing algorithms for the design of general mammal @-@ specific , and virus @-@ specific siRNAs that are automatically checked for possible cross @-@ reactivity . 
