Self-modifying RNA molecules and methods of making

A method for producing a self-modifying RNA molecule which binds a first ligand and carries out a chemical reaction modifying said self-modifying RNA molecule, comprising the steps of:

• a) providing a first population of RNA molecules comprising RNA molecules having a first region of random sequence;
• b) contacting said first population of RNA molecules with said first ligand;
• c) isolating a first ligand-binding subpopulation of said first population of RNA molecules by partitioning RNA molecules in said first population which specifically bind said first ligand from those which do not;
• d) amplifying said first ligand-binding subpopulation in vitro;
• e) identifying a first ligand binding RNA sequence present in said amplified first ligand-binding subpopulation;
• f) preparing a second population of RNA molecules comprising RNA molecules comprising said first ligand binding sequence and a second region of random sequence;
• g) contacting said second population of RNA molecules with a second ligand which binds said first ligand binding sequence, said contacting occurring under conditions which allow said second ligand to participate in a chemical reaction which modifies an RNA molecule in said second population;
• and
• h) isolating a subpopulation of said self-modifying RNA molecules from said population of RNA molecules by partitioning RNA molecules which have been modified in step g) from those which have not been modified.