Use of base-modified deoxynucleoside triphosphates to...

C - Chemistry – Metallurgy – 12 – Q

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Details

C12Q 1/68 (2006.01) C12P 19/34 (2006.01) C07H 19/10 (2006.01) C07H 19/20 (2006.01)

Patent

CA 2650820

Aspects of the invention provide novel and surprisingly effective methods for the detection of nucleic acids, comprising nucleic acid amplification using base-modified deoxynucleoside 5'-triphosphates (dNTPs). Particular aspects relate to methods for enhancing hybridization properties of oligonucleotide primers and probes in assays detecting nucleic acids, comprise amplifying target DNAs in presence of base-modified duplex-stabilizing deoxyribonucleoside 5'-triphosphates to provide for modified target DNAs, and thereby considerably improving performance of the detection assays. The disclosed methods allow for increasing of the reaction temperature in PCR-based detection systems or, alternatively, reducing the length of the oligonucleotide primers and probes. Certain aspects relates to improvement of real time PCR assays, wherein nucleic acids of interest are detected as the reaction proceeds using fluorescent agents or oligonucleotide FRET probes.

Par certains aspects, l'invention concerne des méthodes nouvelles et étonnamment efficaces de détection d'acides nucléiques par amplification de ces derniers au moyen désoxynucléoside 5'-triphosphates de désoxynucléoside (dNTP) à base modifiée. En particulier, l'invention porte sur des méthodes accentuant les propriétés d'hybridation d'amorces et de sonde d'oligonucléotide lors d'essais de détection d'acides nucléiques. Ces méthodes consistent à amplifier des ADN cibles en présence de désoxyribonucléoside 5'-diphosphates à stabilisation de double hélice, à base modifiée, dans le but d'obtenir des ADN cibles modifiés, ce qui améliore grandement les performances des essais de détection. Elles permettent d'augmenter la température de réaction des systèmes de détection PCR ou, en variante, de réduire la longueur des amorces et des sondes d'oligonucléotide. Certains aspects concernent une amélioration du temps réel des essais PCR, les acides nucléiques d'intérêt étant détectés en cours de réaction au moyen d'agents fluorescents ou de sondes FRET d'oligonucléotide.

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