Abstract: Provided is a chip process of gene synthesis, and the process comprises incorporating the whole procedure, which comprises amplifying oligonucleotides and assembling the oligonucleotides into a gene in parallel, onto a single chip. A specific mismatch endonuclease is also used in the process to establish an error repair system in gene synthesis, and the error rate is decreased to about 0.19 mismatched bases/kb. The high-throughput, high-fidelity and low-cost chip process of gene synthesis provided in the present invention can meet the requirements of gene synthesis and the optimization and screening of protein expression on a large scale at the frontier of life sciences such as synthetic biology, genomics, and systems biology.

Abstract: Provided is a chip process of gene synthesis, and the process comprises incorporating the whole procedure, which comprises amplifying oligonucleotides and assembling the oligonucleotides into a gene in parallel, onto a single chip. A specific mismatch endonuclease is also used in the process to establish an error repair system in gene synthesis, and the error rate is decreased to about 0.19 mismatched bases/kb. The high-throughput, high-fidelity and low-cost chip process of gene synthesis provided in the present invention can meet the requirements of gene synthesis and the optimization and screening of protein expression on a large scale at the frontier of life sciences such as synthetic biology, genomics, and systems biology.

Abstract: A method of synthesizing a nucleic acid molecule, such as a gene, on a substrate or microchip is described. In particular, a method for synthesizing, amplifying, and assembling DNA oligonucleotides into a nucleic acid molecule or gene product, on a single substrate or microchip is described. Also described are a method of correcting a sequence error in a synthesized nucleic acid molecule, as well as a method for synthesizing and screening a library of codon variants to identify a nucleic acid molecule with an optimized level of protein expression.

Abstract: An enzymatic method for removing sequence errors in nucleic acid molecules are described. The method utilizes a CEL endonuclease that cuts heteroduplexes at mismatch sites containing the errors and an overlap extension polymerase chain reaction to re-assemble the cleaved fragments into full-length nucleic acid molecules free of the errors.

Abstract: Provided is a chip process of gene synthesis, and the process comprises incorporating the whole procedure, which comprises amplifying oligonucleotides and assembling the oligonucleotides into a gene in parallel, onto a single chip. A specific mismatch endonuclease is also used in the process to establish an error repair system in gene synthesis, and the error rate is decreased to about 0.19 mismatched bases/kb. The high-throughput, high-fidelity and low-cost chip process of gene synthesis provided in the present invention can meet the requirements of gene synthesis and the optimization and screening of protein expression on a large scale at the frontier of life sciences such as synthetic biology, genomics, and systems biology.

Abstract: A method of synthesizing a nucleic acid molecule, such as a gene, on a substrate or microchip is described. In particular, a method for synthesizing, amplifying, and assembling DNA oligonucleotides into a nucleic acid molecule or gene product, on a single substrate or microchip is described. Also described are a method of correcting a sequence error in a synthesized nucleic acid molecule, as well as a method for synthesizing and screening a library of codon variants to identify a nucleic acid molecule with an optimized level of protein expression.

Abstract: An enzymatic method for removing sequence errors in nucleic acid molecules are described. The method utilizes a CEL endonuclease that cuts heteroduplexes at mismatch sites containing the errors and an overlap extension polymerase chain reaction to re-assemble the cleaved fragments into full-length nucleic acid molecules free of the errors.

Abstract: Methods of improving the kinetics of bimolecular interactions where reactants are present in low concentrations are provided. Methods of pre-amplifying one or more oligonucleotides using high concentration universal primers are provided. Methods of improving the error rate in oligonucleotide and/or polynucleotide syntheses are also provided. Methods for sequence optimization and oligonucleotides design are further provided.