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Title: Method for in vitro recombination

Patent ·
OSTI ID:1531645

The present invention relates, e.g., to an in vitro method, using isolated protein reagents, for joining two double-stranded (ds) DNA molecules of interest, wherein the distal region of the first DNA molecule and the proximal region of the second DNA molecule share a region of sequence identity, comprising (a) chewing back the DNA molecules with an enzyme having an exonuclease activity, to yield single-stranded overhanging portions of each DNA molecule which contain a sufficient length of the region of sequence identity to hybridize specifically to each other; (b) specifically annealing the single-stranded overhangs; and (c) repairing single-stranded gaps in the annealed DNA molecules and sealing the nicks thus formed (ligating the nicked DNA molecules). The region of sequence identity generally comprises at least 20 non-palindromic nucleotides (nt), e.g., at least about 40 non-palindromic nt. In some embodiments of the invention, about 5% PEG is present during all steps of the reaction, and/or the repair reaction is achieved with Taq DNA polymerase and a compatible ligase, such as Taq DNA ligase. The method allows the joining of a number of DNA fragments, in a predetermined order and orientation, without the use of restriction enzymes. It can be used, e.g., to join synthetically produced sub-fragments of a gene or genome of interest.

Research Organization:
Synthetic Genomics, Inc., San Diego, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG02-02ER63453
Assignee:
Synthetic Genomics, Inc. (San Diego, CA)
Patent Number(s):
7,776,532
Application Number:
11/502,624
OSTI ID:
1531645
Resource Relation:
Patent File Date: 2006-08-11
Country of Publication:
United States
Language:
English

References (27)

Process for in vitro creation of recombinant polynucleotide sequences by oriented ligation patent January 2006
Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC journal February 2007
Seamless gene engineering using RNA- and DNA-overhang cloning journal July 2000
Nucleic Acid Cloning patent-application September 2005
In Vivo Gene Transfer patent-application December 2003
Yeast artificial chromosomes (YACs) and the analysis of complex genomes journal January 1992
Directional cloning patent December 1991
Biochemical effects of molecular crowding journal November 2004
Method for the complete chemical synthesis and assembly of genes and genomes patent February 2003
Stimulation of enzymatic ligation of DNA by high concentrations of nonspecific polymers patent April 1986
High-throughput, genome-scale protein production method based on the wheat germ cell-free expression system journal November 2003
Recombinase Polymerase Amplification patent-application May 2005
Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors journal May 1987
Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases. journal July 1993
Recombineering with overlapping single-stranded DNA oligonucleotides: Testing a recombination intermediate journal May 2003
RecE/RecT and Redα/Redβ initiate double-stranded break repair by specifically interacting with their respective partners journal August 2000
Methods and kits for recombining nucleic acids patent November 2000
Functional cloning vectors for use in directional cDNA cloning using cohesive ends produced with T4 DNA polymerase journal March 1992
Joining of long double-stranded RNA molecules through controlled overhangs journal October 2004
Directional cloning of PCR products using exonuclease III journal January 1992
Ligation independent cloning irrespective of restriction site compatibility journal October 1997
Construction of recombinant DNA by exonuclease recession journal January 1993
Evolution of whole cells and organisms by recursive sequence recombination patent April 2002
Cloning of PCR products after defined cohesive termini are created with T4 DNA polymerase journal January 1990
Efficient total gene synthesis of 1.35-kb hybrid alpha-lytic protease gene using the polymerase chain reaction. journal February 1993
Generating a synthetic genome by whole genome assembly: φX174 bacteriophage from synthetic oligonucleotides journal December 2003
Single-step assembly of a gene and entire plasmid from large numbers of oligodeoxyribonucleotides journal October 1995

Cited By (7)

Assembly of large nucleic acids patent March 2017
Fusion polymerase and method for using the same patent May 2018
Synthon formation patent September 2016
Synthesis of long nucleic acid sequences patent June 2017
In vitro recombination methods using 5′ exonuclease patent January 2016
High throughput sequencing of end regions of long linear DNAs patent April 2018
Efficient and rapid method for assembling and cloning double-stranded DNA fragments patent April 2018