Abstract
Directed evolution was first applied to diverse libraries of DNA and RNA molecules a quarter century ago in the hope of gaining technology that would allow the creation of receptors, ligands, and catalysts on demand. Despite isolated successes, the outputs of this technology have been somewhat disappointing, perhaps because the four building blocks of standard DNA and RNA have too little functionality to have versatile binding properties, and offer too little information density to fold unambiguously. This review covers the recent literature that seeks to create an improved platform to support laboratory Darwinism, one based on an artificially expanded genetic information system (AEGIS) that adds independently replicating nucleotide “letters” to the evolving “alphabet”.
Highlights
More than a quarter century ago, Larry Gold, Jack Szostak, Gerald Joyce, Andrew Ellington, and others offered the promise of a process that would rapidly create receptors, ligands, and catalysts on demand [1,2]
All that was necessary was to create a library of nucleic acids, subject that library to processes by which species would be extracted that had some of the binding or catalytic activity desired, copy these “survivors” by PCR, possibly introducing mutations from species that had a low level of the desired activity, allowing improvement by locally searching the sequence space around such an individual, and repeating this process of selection/amplification until DNA or RNA binders or enzymes emerged with specifications that were adequate for the desired application
This hope was greatly magnified by the view that life on Earth itself had experienced an episode of natural history where nucleic acids were the only genetically encoded compounds of biological catalysis, performing many of the roles that are performed by proteins [3,4]
Summary
More than a quarter century ago, Larry Gold, Jack Szostak, Gerald Joyce, Andrew Ellington, and others offered the promise of a process that would rapidly create receptors, ligands, and catalysts on demand [1,2]. Inaccessible to natural biopolymers, the functional groups need not be constrained to those that have been delivered to us by prebiotic chemistry and natural history; should chemical theory direct, they may include groups that manage the intrinsic difficulties of binding targets or catalyzing difficult reactions, such as cleaving peptide bonds. AEGIS is a biopolymer similar to DNA with donor and acceptor groups, forming orthogonal nucleobase pairs They [62,63,64], resemblebut natural building blocks, in and turnpairing creates the opportunity attach a number of functional groups nucleotides in size,which shape, geometries, are to independently replicable, and they dothat not might be useful in binding even catalysis.that. A nucleic acid molecule a given length, the potential to increase functionality
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
