Process for site specific mutagenesis without phenotypic selecti

Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or... – Modification of viruses

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435 6, 435 68, 435 91, 4351721, 4353171, 435320, 935 10, 935 16, 536 27, C12N 1500, C12N 700, C12P 2100, C12P 1934

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048731927

ABSTRACT:
The present invention discloses several DNA mutagenesis processes using a DNA template containing several uracil residues in place of thymine, which can be applied without selection techniques to produce altered DNA sequences with approximately 10-fold greater efficiency than current methods of site-specific mutagenesis.
This template has relatively normal coding potential in the in vitro reactions typical of standard site-directed mutagenesis protocols but is not biologically active upon transfection into a wild type (i.e., ung.sup.+) E. coli host cell. Expression of a desired change, present in the newly synthesized non-uracil-containing covalently closed circular complementary strand, is thus favored. The procedure has been applied to mutations introduced via both obligonucleotides and error-prone polymerization. The inclusion of two additional simple treatment steps before transfection results in a site-specific mutation frequency approaching 100%.

REFERENCES:
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Kunkel, PNAS, vol. 81, pp. 1494-1498 (1984).

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