IDT Reduces Undesirable Effects of RNAi Protocols

Integrated DNA Technologies (IDT) will present two keynote addresses at the upcoming RNAi International Conference and Exhibition and its co-hosted symposium, Aptamers.

Providing a forum for the discussion of long and short non-coding RNAs, their role in gene regulation, functional studies, RNA biomarkers and therapeutic application, IDT CSO Dr Mark Behlke will share IDT’s expertise within the advancing field of RNAi.

Forming part of the Aptamers track (24-25 March), Dr Behlke will discuss how aptamers can be employed as a targeting ligand to deliver therapeutic cargo to specific cell types. Such cargo can be attached following aptamer synthesis using reactive chemistries or through hybridization to a ‘stick’ domain.

Attachment using the ‘stick’ domain is highly flexible and allows the use of a broad variety of cargo types. However the addition of the ‘anti-stick’ sequence to facilitate release of the cargo can prove problematic, with reduced siRNA potency often experienced. Design considerations to minimize these undesirable effects will therefore be explored.

Off-target effects are a chronic problem for studies employing RNAi, since the seed region directs suppression of unknown targets via miRNA. Bioinformatic methods have been developed, however a 7mer seed region has thousands of possible binding sites and it is extremely difficult to predict which of these are significant. Chemical methods can reduce the incidence of these effects, but will cause a reduction in the potency of the siRNA.

During RNAi (25-27 March), Dr Behlke will discuss Unlocked Nucleic Acids (UNAs), which have previously been proven useful in the reduction of off-target effects while retaining potency.

This presentation will cover the use of UNAs in Dicer-substrate siRNAs (DisRNA), comparing position-specific UNA effects on seed region off-target effects and potency.