Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation

A method for identifying a oligonucleotides and reverse complement having activity against a target, comprising:

• generating a set of candidate sequences of oligonucleotides and reverse complements having a predetermined length, wherein the set comprises the set of all sequences having the predetermined length that are complementary to the target sequence;
• calculating for the set members at least one of a thermodynamic property score, a sequence property score, and a homology property score;
• retaining within the set members having the at least one score within a desired score range;
• synthesizing the retained set members;
• and
• assaying the retained set members for activity against the target, wherein the assay is indicative of an amount of an mRNA or a protein encoded by the target.

A method comprising:

• receiving an in silico oligonucleotide and reverse complement from an input means;
• receiving at least one prescribed property of the oligonucleotide and reverse complement from the input means;
• selecting a modification for generating a modified oligonucleotide and reverse complement;
• generating in silico the modified oligonucleotide and reverse complement having the prescribed property and selected nucleobase modification;
• and
• communicating the in silico modified oligonucleotide and reverse complement to an output means.

A method comprising:

• receiving an in silico oligonucleotide and reverse complement to be synthesized having a prescribed property from an input means;
• generating synthesis instructions adapted to a synthesizer;
• and
• communicating the synthesis instructions to the synthesizer thereby providing the oligonucleotide and reverse complement to be synthesized.

A method comprising:

• providing a group of properties which define a target oligonucleotide and reverse complement and from which group a sub-group is selected;
• receiving the selected sub-group of properties according to a user selection;
• generating in silico, a oligonucleotide and reverse complement having the selected sub-group of properties;
• determining in silico, synthesis instructions for the oligonucleotide and reverse complement;
• and
• communicating the synthesis instructions to a synthesizer.

A method comprising:

• receiving an in silico oligonucleotide and reverse complement to be synthesized having a prescribed property, a threshold criteria, and a user defined target from an input means;
• analyzing in silico the oligonucleotide and reverse complement according to the prescribed property, the threshold criteria, and the target thereby producing an analysis report;
• and
• communicating the analysis report to an output means.

A method of selecting a oligonucleotide and reverse complement from a library of oligonucleotide and reverse complement according to user selection criterion comprising:

• receiving a target through an input means according to a user selection;
• receiving the user selection criterion, where the user criterion is a property selected from the group comprising a chemical property, a physical property, and a biological property, wherein each property is in relation to the oligonucleotide and reverse complement of the library of oligonucleotide and reverse complement;
• obtaining a threshold activity level and a test assay;
• comparing a plurality of oligonucleotide and reverse complement of the library to the target according to the test assay, thereby determining a rank for each compared oligonucleotide and reverse complement of the library;
• grouping in an active set the oligonucleotide and reverse complement having rank greater than the threshold activity level;
• and
• communicating the active set to an output means.

A method of designing a oligonucleotide and reverse complement comprising:

• receiving a target nucleic acid sequence;
• receiving a defined criteria for at least one nucleobase of the oligonucleotide and reverse complement;
• receiving a prescribed set of properties comprising a physical property, a chemical property, or a biological property of the oligonucleotide and reverse complement to be designed;
• generating a oligonucleotide and reverse complement design according to the prescribed set of properties and the target nucleic acid sequence;
• generating in silico a oligonucleotide and reverse complement according to the oligonucleotide and reverse complement design;
• and
• communicating the in silico oligonucleotide and reverse complement to an output means.