Single-stranded oligodeoxynucleotide mutational vectors

Details Single-stranded oligodeoxynucleotide mutational vectors Single-stranded oligodeoxynucleotide mutational vectors

A - Human Necessities

61

K

A61K 48/00 (2006.01) C07H 21/04 (2006.01) C12N 15/10 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2382120

The invention concerns the introduction of predetermined genetic changes in target genes of a living cell by introducing an oligodeoxynucleotide encoding the predetermined change. The oligodeoxynucleotides are effective in animal, plant and bacterial cells. Specific end modifications that greatly increase the effectiveness of the oligodeoxynucleotides in bacteria are described. Surprisingly, unmodified oligodeoxynucleotides can be as effective in mammalian cells, including in vivo hepatocytes, as the modified nucleotides and can be as effective or more effective than chimeric oligonucleotides that consist of a mixture of deoxynucleotides and 2'-O-methyl ribonucleotides.

L'invention concerne l'introduction de modifications génétiques prédéterminées dans des gènes cibles d'une cellule vivante, par introduction d'oligodéoxynucléotides codant pour la modification prédéterminée. Les oligodéoxynucléotides sont efficaces chez les animaux, les plantes et les cellules bactériennes. L'invention concerne également des modifications spécifiques de terminaison augmentant grandement l'efficacité des oligodéoxynucléotides dans les bactéries. On a découvert avec surprise que les oligodéoxynucléotides non modifiés peuvent être aussi efficaces dans des cellules de mammifères, notamment des hépatocytes in vivo, que des nucléotides modifiés, et peuvent être aussi efficaces, voire plus, que des oligonucléotides chimériques constitués d'un mélange de déoxynucléotides et de 2'-O-méthyl ribonucléotides.

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