Chimeric mutational vectors having non-natural nucleotides

Details Chimeric mutational vectors having non-natural nucleotides Chimeric mutational vectors having non-natural nucleotides

C - Chemistry, Metallurgy

12

N

C12N 15/90 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C12N 15/10 (2006.01) C12N 15/79 (2006.01) C12N 15/82 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2258090

The application concerns the design and use of small, duplex oligonucleotides and oligomers of nucleotide analogs, termed Chimeric Mutational Vectors (CMV) to effect mutation in a target gene of a eukaryotic cell by homologous recombination between the CMV and the target. The CMV comprises ribonucleotides and deoxyribonucleotides and nucleotide analogs of each (generically "nucleobases"). The application discloses that CMV contain at least two segments of at least 3 ribo-type nucleobases paired to deoxyribo- type nucleobases, which regions flank the region of the CMV that corresponds to the mutation to be introduced into the target gene. The ribo-type nucleobases should preferably be nuclease resistant i.e., other than naturally occurring ribonucleotides. The uses of CMV include gene therapy of genetic diseases and construction of transgenic plants and animals.

La demande concerne la conception et l'utilisation de petits oligonucléotides duplex et d'oligomères d'analogues nucléotidiques, appelés vecteurs mutationnels chimères (CMV) afin de procéder à la mutation dans un gène cible d'une cellule eucaryote par recombinaison homologue entre le CMV et la cible. Le CMV comprend des ribonucléotides et des désoxyribonucléotides ainsi que des analogues nucléotidiques de chacun (génériquement "nucléobases"). La demande fait état du fait que le CMV contient au moins deux segments d'au moins 3 nucléobases de type ribo apariés à des nucléobases de type désoxyribo, lesquelles régions bordent la région du CMV correspondant à la mutation à introduire dans le gène cible. Les nucléobases de type ribo doivent de préférence être résistants aux nucléases c'est-à-dire des ribonucléotides non naturels. Les utilisations de CMV comprennent la thérapie génique de maladies génétiques et la construction de plantes et d'animaux transgéniques.

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