The beauty of the siPool

The siPool strategy is beautifully simple:

By having many on-target siRNAs, each with a different seed sequence, you maintain on-target efficiency while diluting out off-target effects.

One analogy is the beauty of composite faces.

Which of these faces do you find most attractive?

If you’re like most people, you will have chosen the last face, which is actually a composite of the other 5 faces (source).

Each individual face has its flaw(s).  Spock ears, mildly everted lips, incongruous eyebrows, etc.  No face is ideal.  But when combined, these flaws are evened out.

Same thing with siRNAs.  Each individual siRNA has its own ugly off-target signature.  But combined in a high-complexity siPool, the off-target warts are removed, and you’re left with a beautiful on-target phenotype.

And not all facial averages are equal.  Perrett et al. found that a composite face created from faces pre-selected as being more attractive was preferred  over a composite created from all available faces.

Likewise, siPools are composed of the best available individual siRNAs.

Being selective about what goes into a siPool is important, as we will discuss more in future posts.

This amusing anectdote from the autobiography of Francis Galton is à propos.  (Galton pioneered composite facial analysis, in addition to finger print analysis, as discussed previously)


I could not make good composites of lunatics ; 
their features are apt to be so irregular in different 
ways that it was impossible to blend them. I took a 
photographer with me to Hanwell, where it was 
arranged that the patients should sit two at a time on 
a bench. One of them was to be led forward and 
posted in front of the camera, while his place on the 
bench was filled by the second patient moving up 
into it, whose previous place was to be occupied by a 
third patient It happened that the second of the 
pair who were the first to occupy the bench considered 
himself to be a very mighty man, I forget whom, but 
let us say Alexander the Great. He boiled with 
internal fury at not being given precedence, and when 
the photographer had his head well under the velvet 
cloth, with his body bent, in the familiar attitude of 
photographers while focusing, Alexander the Great 
slid swiftly to his rear and administered a really good 
bite to the unprotected hinder end of the poor 
photographer, whose scared face emerging from 
under the velvet cloth rises vividly in my memory as 
I write this. The photographer guarded his rear 
afterwards by posting himself in a corner of the 

Memories of My Life, pp 262-263


Don’t get bitten by bad RNAi reagents.

Please see our website for more information on siPools technology.