Small-molecule mediated size selection of nucleic acids

A method of selectively isolating target nucleic acid molecules from a nucleic acid-containing sample, wherein the target nucleic acid molecules are within a particular molecular size range and non-target nucleic acid molecules are outside the molecular size range, comprising:

• a) contacting a sample comprising nucleic acid molecules with a first matrix in the presence of a first small-molecule modulator, wherein
• the first small-molecule modulator is present in a sufficient concentration that the target nucleic acid molecules selectively bind to the first matrix and non-target nucleic acid molecules do not bind to the first matrix,
• increasing the concentration of the small-molecule modulator increases the molecular weight cut-off for nucleic acid molecules that bind to the matrix, and
• the first small-molecule modulator
• (1) is of formula (Ib) or a hydrate thereof:
• (R2)nMn+ (Ib)
• wherein R2 is a phosphate or a phosphonic acid;
• M is a metal or N(Ra)4;
• each Ra is independently H or alkyl;
• and
• n is 1, 2, or 3;
• or
• (2) is a carboxylate compound of formula (I) or a hydrate thereof
• wherein R is selected from the group consisting of H, unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 alkenyl, and substituted or unsubstituted C1-C8 alkynyl;
• M is a metal or N(Ra)4;
• each IV is independently H or alkyl;
• and
• n is 1, 2, or 3.