= Systematic evolution of ligands by exponential enrichment
= SELEX
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\b[Systematic evolution of ligands by exponential enrichment], abbreviated \b[<SELEX>], is an <in vitro selection> strategy that repeatedly selects binding <nucleic acid> variants and amplifies their recoverable sequences. In an <RNA> implementation, a sequence pool is transcribed, exposed to a target, partitioned into retained and unretained material, and regenerated through <reverse transcription>, <polymerase chain reaction> and renewed <transcription>. A binding molecule recovered by this process can be an <aptamer>.
The 1990 experiment by <C. Tuerk> and <L. Gold> randomized eight positions in an <RNA> region associated with <bacteriophage T4 DNA polymerase>, defining $4^8=65{,}536$ possible sequences. Repeated binding selection and amplification recovered preferred variants.<Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase by C. Tuerk and L. Gold>[Primary abstract: target, randomized region and selection/amplification cycle]{ref} Gold's firsthand retrospective connects the name and experimental design to this work.<SELEX: How It Happened and Where It will Go by Larry Gold>[The First Moments]{ref}
An original equilibrium model explains a practical tradeoff. With free target concentration $T$ maintained approximately constant and single-site <dissociation constants> $K_A,K_B$, ideal binding fractions are
$$
s_A=\frac{T}{K_A+T},\qquad s_B=\frac{T}{K_B+T},\qquad
\frac{s_A}{s_B}=\frac{K_B+T}{K_A+T}.
$$
For stipulated $K_A=1$ nM and $K_B=100$ nM, target at 10 nM gives binding fractions about 0.909 and 0.0909: tenfold relative retention. At 1 nM they become 0.5 and approximately 0.00990: 50.5-fold relative retention. Lowering target strengthens discrimination in this model but also loses more desired molecules. This is the <target-concentration tradeoff in affinity selection>.
If the desired class starts at fraction $p$, its ideal post-selection fraction is $ps_A/[ps_A+(1-p)s_B]$, assuming equal subsequent amplification. For $p=0.001$, the two target concentrations above give approximately 0.00991 and 0.04812. These constructed values are not yields from the historical experiment, and the model excludes target depletion, kinetic wash losses and sequence-dependent amplification.
Enrichment therefore measures success in the whole selection protocol. Binding to a support, survival through washing or preferential amplification can change sequence abundance without improving the intended <binding affinity>. Independent binding measurements and appropriate control selections distinguish those mechanisms from target recognition. Iteration is powerful because it makes rare sequences recoverable, while also repeatedly applying every bias in the experimental cycle.
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