Abstract: The disclosure describes methods that include providing a first nucleic acid having a sequence encoding a first set comprising one or more transcription activator-like effector (TALE) repeat domains and/or one or more portions of one or more TALE repeat domains; contacting the first nucleic acid with a first enzyme, wherein the first enzyme creates a first ligatable end; providing a second nucleic acid having a sequence encoding a second set comprising one or more TALE repeat domains and/or one or more portions of one or more TALE repeat domains; contacting the second nucleic acid with a second enzyme, wherein the second enzyme creates a second ligatable end, and wherein the first and second ligatable ends are compatible; and ligating the first and second nucleic acids through the first and second ligatable ends to produce a first ligated nucleic acid, wherein the first ligated nucleic acid is linked to a solid support, and wherein the first ligated nucleic acid encodes a polypeptide comprising said first and

Abstract: A method of designing a multi-zinc-finger polypeptide predicted to bind to a sequence of interest that has at least three subsites includes the steps of: a) providing a nucleotide sequence of interest having first, second, and third consecutive subsites, wherein each of the first and third subsites are adjacent to the second subsite; b) identifying first and second adjacent zinc finger polypeptide sequences previously shown to bind to the first and second subsites in the context of a multi-zinc finger polypeptide; c) identifying a third zinc finger polypeptide previously shown to bind to a third subsite adjacent to the second subsite when present in the context of a multi-zinc finger polypeptide adjacent to the second zinc finger polypeptide; and d) combining the first, second, and third zinc finger polypeptide sequences in linear order, thereby designing a multi-zinc finger polypeptide predicted to bind to the sequence of interest.