Cover Story: It is an RNA world

Box 2. Considerations for compelling target and therapeutic validation.

· Empirical validation that the lncRNA target is expressed in the right place at the right time to impact the disease

·The target has distinct upregulated and downregulated states

· The therapeutic modulates the target in a sequence-specific manner

· An immune response has been ruled out

· The therapeutic binds the target

· Gene expression changes in response to the therapeutic

· An intact copy of the target human gene to be upregulated is present in the population with the disease

· The therapeutic effect is reproducible, considering both the variability of the analyte and the model system

· The delivery vehicle(s) for controls are pharmacokinetically comparable to the vehicle for the therapeutic

· A reliable tool (biomarker) to distinguish between target engagement and no engagement or target response and no response in vivo is available and utilized