PROGRAMMABLE ITERATED ELONGATION: A METHOD FOR MANUFACTURING SYNTHETIC GENES AND COMBINATORIAL DNA AND PROTEIN LIBRARIES

摘要

A method for manufacturing synthetic genes and combinatorial DNA and protein libraries, termed here Divide and Conquer-DNA synthesis (D&C-DNA synthesis) method. The method can be used in a systematic and automated way to synthesize any long DNA molecule and, more generally, any combinatorial molecular library having the mathematical property of being a regular set of strings. The D&C-DNA synthesis method is an algorithm design paradigm that works by recursively breaking down a problem into two or more sub-problems of the same type. The division of long DNA sequences is done in silico. The assembly of the sequence is done in vitro. The D&C-DNA synthesis method protocol consists of a tree, in which each node represents an intermediate sequence. The internal nodes are created in elongation reactions from their daughter nodes, and the leaves are synthesized directly. After each elongation only one DNA strand passes to the next level in the tree until receiving the final product. Optionally and preferably, error correction is performed to correct any errors which may have occurred during the synthetic process.

主权项

1. A system for at least semi-automatically manufacturing a polymer, comprising:
(a) a first computational device for operating a language program for specifying a plurality of polymers and for deconstructing said plurality of polymers into a plurality of potentially faulty subcomponents of said plurality of polymers according to a hierarchical deconstruction protocol, such that the polymers are constructable from said plurality of potentially faulty subcomponents according to a hierarchical construction protocol; (b) a second computational device for operating a program for constructing said polymers according to said hierarchical construction protocol, said program directing synthesis of a plurality of polymer molecules from said potentially faulty subcomponents and said program forming a robot control program for executing synthesis of the polymers, wherein said robot control program comprises said hierarchical construction protocol; (c) a database for storing a plurality of synthetic schemes for synthesizing said polymers, a list of subcomponents for synthesizing said polymers, a model of the biochemical process of said polymer synthesis for determining cost of synthesis of the polymers, wherein said program determines said cost according to said model, selects one of said synthetic schemes according to said cost and directs the synthesis of the polymers; (d) a storage for storing a library of potentially faulty subcomponents, comprising physical molecules corresponding to said plurality of potentially faulty subcomponents from said deconstructing by said first computational device; and (e) a robot for being controlled by said robot control program of said second computational device and for synthesizing the polymer from said polymer molecules and said library of potentially faulty subcomponents according to said hierarchical construction protocol, wherein said hierarchical construction protocol potentially comprises an error correction protocol.