Importance

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Abstract

The invention provides a method of convergently synthesizing mixtures of either single stranded or double stranded polynucleotides. In one aspect, oligonucleotides that form components of such polynucleotides are synthesized on one or more microarrays, or other large-scale parallel solid phase synthesis platforms, after which they are amplified directly, or are released into solution and then amplified. At least two sets of such released and amplified oligonucleotides are produced, referred to herein as first and second amplicons. The first and second amplicons are cleaved and then ligated to different ends of a bridging duplex that is present in the reaction in limiting quantity to form a polynucleotide mixture of the invention. At the completion of the reaction, each polynucleotide in the mixture is present in substantially equal concentration, regardless of the starting concentrations of the first and second amplicons. That is, the invention provides a method for synthesizing a normalized mixture of polynucleotides.

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First Claim