Abstract: The present invention provides for a method for producing a cDNA library enriched for rare cDNAs and reduced in abundant cDNAs which comprises: (a) obtaining a pool of linear double-stranded cDNAs; (b) cloning a first portion of the pool of cDNAs into a first vector to create a first cDNA library; (c) cloning a second portion of the pool of cDNAs into a second vector to create a second cDNA library; (d) producing single-stranded linear cDNA inserts (target cDNA) from the first cDNA library; (e) producing single-stranded circles (target cDNA) from the second cDNA library; (f) producing a pool of abundant linear cDNAs (driver cDNA) from the first and the second DNA libraries; (g) hybridizing the linear cDNA inserts from step (d) or the single-stranded circles from step (e) with an excess amount of the abundant cDNA pool produced from the second cDNA library or the first cDNA library, respectively, from step (f) under hybridization conditions to produce duplexes, and (h) isolating single-stranded linear cDNA ins