Oligonucleotides labeled with stable isotopes and a method for detecting the same

Abstract

Antisense oligonucleotide sequences which enable the measurement of the distribution and structure of antisense oligonucleotide drugs in the body, with lapse of time, and a method of detecting these sequences are provided. The antisense chains have a natural or non-natural nucleotide or peptide nucleic acid as a structural unit in which carbon atoms and nitrogen atoms are substituted by 13C and 15N, respectively, and the antisense chains can be detected by nuclear magnetic resonance spectroscopy (NMR) such as 15N—1H or 13C—1H hereto nuclear multiple quantum coherence spectroscopy.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the priority benefit of Japanese application serial no. 11 -094323, filed Mar. 31, 1999. BACKGROUND OF THE INVENTION [0002] 1. Technical Field of the Invention [0003] The present invention relates to methods for detecting antisense oligonucleotides and peptide nucleic acids which are labeled with stable isotopes, and foreign antisense chains. [0004] 2. Background of the Invention [0005] In recent years, antisense drugs using antisense technology have drawn attention as therapeutic agents for diseases such as cancers, genetic diseases and AIDS. An antisense drug refers to an oligonucleotide or the like that has a sequence complementary (antisense) to a part of a sequence of a specific gene which causes a certain disease. When introduced into the body (target cells), the antisense drug forms a specific double strand chain with mRNA, which is a transcription product of the causative gene, or a precursor thereof, to i...

AI Technical Summary

Benefits of technology

[0009] The present invention was made in consideration of the abovementioned problem and an objective of the present invention is to provide antisense oligonucleotide sequences and antisense peptide nucleic acid sequences labeled with stable isotopes, which enables the measurement of the distribution, state of conservation and structure of antisense oligonucleotide drugs in the body, with the lapse of time, and a method of detecting these sequences.

Problems solved by technology

However, conventional pharmacokinetic tests using radioisotopes or the like provide information on the distribution in the body, absorption rate, and excretion rate of the oligonucleotides but not on the conservation of their sequence and length.

Furthermore, it was virtually impossible to see the change in the length of the administered antisense nucleotides with the lapse of time (the progress of decomposition).

Further, there is no means to confirm whether the target mRNA or precursor mRNA and the oligonucleotide introduced into cells form complementary double strand chains.

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