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Recent achievements in therapeutic oligonucleotide chemistry

ANDREI LAIKHTER
Chief Scientific Officer, Chemgenes Corporation

In recent times both basic and applied molecular biology studies have made extensive use of modified oligonucleotides as tools in the study of gene regulation and drug discovery. In particular, modified oligonucleotides have been used in applications such as antisense gene regulation and in different hybridization-based assays.

 

ANTISENSE AND EXON SKIPPING TECHNOLOGIES
Many modified oligonucleotides have been used as antisense molecules, targeting mRNA for the study of gene regulation. These DNAs or their analogues can hybridize to the complementary region of a corresponding DNA or RNA and affect gene expression. For antisense molecules that target mRNA, gene expression is suppressed by Rnase H catalyzed cleavage of the bound mRNA of the duplex. When one is designing oligonucleotide molecules for antisense studies, there are three major considerations. The affinity and stability of heteroduplexes of mRNA with DNA or its modified analog should be taken into account. Furthermore, one must consider the vulnerability of the molecule to nuclease activity. Finally, a characteristic important for in vivo study i ...




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