Methods for the integrated synthesis and purification of oligonucleotides

A method for the synthesis and purification of oligonucleotides comprising the steps of:

• (a) synthesizing an oligonucleotide pursuant to standard techniques for solid phase oligonucleotide synthesis (SPOS), wherein during the capping step of each synthetic cycle a cap derivatized with a moiety capable of undergoing a cycloaddition reaction is introduced to unreacted terminal functional groups of the growing oligonucleotide chain which failed to be elongated in the preceding coupling step, wherein the corresponding capping agent comprises functional groups A and B, functional group A being reactive to terminal functional groups of the oligonucleotide and functional group B being able to participate in a cycloaddition reaction;
• (b) cleaving the oligonucleotide from the solid phase synthesis support, and, either deprotecting the oligonucleotide compound completely, or deprotecting the oligonucleotide compound completely except for the terminal protective group;
• (c) adding a trapping agent to the product obtained following step 2, wherein said trapping agent is comprised of a solid phase derivatized with functional groups C, wherein the functional groups C are capable of undergoing a cycloaddition reaction with the functional groups B that were part of the capping agent in step (a), and incubating the resulting mixture under conditions of time and temperature that promote a cycloaddition reaction between the functional groups B and C,
• (d) separating the trapping agent from the remainder of the reaction mixture.