Evolving new molecular function
First Claim
3-1. The method of claim 1, wherein the chemical compound syntheiszed is a compound other than a nucleic acid or nucleic acid analog.
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Abstract
Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.
170 Citations
46 Claims
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3-1. The method of claim 1, wherein the chemical compound syntheiszed is a compound other than a nucleic acid or nucleic acid analog.
- 10. A library comprising one or more chemical compounds wherein each of the chemical compounds is bonded to an amplifiable template whose nucleotide sequence is informative of the structure of the chemical compounds.
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12. A method for the synthesis of a library of chemical compounds, the method comprising the steps of:
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providing one or more templates optionally associated with one or more reactive units;
contacting the one or more templates simultaneously or sequentially with one or more transfer units comprising anti-codon units associated with one or more reactive units under condition suitable for hybridization of the anti-codons with the template and reaction of the reactive units to produce a plurality of different library members. - View Dependent Claims (13, 14, 15, 16, 17, 18, 25, 26, 27, 28, 29, 30, 31, 32)
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19. A method for the synthesis of one or more unnatural polymers, the method comprising steps of:
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providing one or more nucleic acid templates;
contacting one or more transfer units with the one or more nucleic acid template under conditions to allow for hybridization and reaction to form bonds between adjacent monomer units lined up along the template. - View Dependent Claims (20, 21, 22)
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24. The method of claim 23, wherein the desired property comprises catalyzing a chemical reaction.
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33. A method of evolving a library of compounds, the method comprising steps of:
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isolating a compound with a desired activity attached to a nucleic acid template that encoded its synthesis;
mutating and amplifying the nucleic acid template; and
synthesizing a new library of related compounds using a mutated and amplified nucleic acid template. - View Dependent Claims (34, 35, 36, 37, 38)
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- 41. A kit comprising one or more nucleic acid templates and one or more transfer units.
Specification