Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites

A computer program product for selecting a target sequence within a polynucleotide for targeting by a zinc finger protein, comprising:

• (a) code for providing a polynucleotide sequence;
• (b) code for selecting a potential target site within the polynucleotide sequence;
• the potential target site comprising first, second and third triplets of bases at first, second and third positions in the potential target site;
• (c) code for calculating a score for the potential target site from a combination of subscores for the first, second, and third triplets, the subscores being obtained from a correspondence regime between triplets and triplet position, wherein each triplet has first, second and third corresponding positions, and each corresponding triplet and position has a particular subscore, the subscore being a value indicating the desirability of the triplet occupying the triplet position, and the correspondence regime being a matrix of subscores for combinations of triplets and triplet positions;
• (d) code for repeating steps (b) and (c) at least once on a further potential target site comprising first, second and third triplets at first, second and third positions of the further potential target site to determine a further score;
• (e) code for providing output of at least one of the potential target site with its score;
• and
• (f) a computer readable storage medium comprising the codes.

A system for selecting a target sequence within a polynucleotide for targeting by a zinc finger protein, comprising:

• (a) a memory;
• (b) a system bus;
• (c) a processor operatively disposed by computer readable storage medium comprising code to:
• (1) provide or receive a polynucleotide sequence;
• (2) select a potential target site within the polynucleotide sequence;
• the potential target site comprising first, second and third triplets of bases at first, second and third positions in the potential target site;
• (3) calculate a score for the potential target site from a combination of subscores for the first, second, and third triplets, the subscores being obtained from a correspondence regime between triplets and triplet position, wherein each triplet has first, second and third corresponding positions, and each corresponding triplet and position has a particular subscore, the subscore being a value indicating the desirability of the triplet occupying the triplet position, and the correspondence regime being a matrix of subscores for combinations of triplets and triplet positions;
• (4) repeat steps (2) and (3) at least once on a further potential target site comprising first, second and third triplets at first, second and third positions of the further potential target site to determine a further score;
• (5) provide output of at least one of the potential target site with its score.